StemCell Therapy

In biology, adipose tissue i, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes.[1] In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ,[2] as it produces hormones such as leptin, estrogen, resistin, and the cytokine TNF. The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. The formation of adipose tissue appears to be controlled in part by the adipose gene. Adipose tissue more specifically brown adipose tissue was first identified by the Swiss naturalist Conrad Gessner in 1551.[3]

In humans, adipose tissue is located beneath the skin (subcutaneous fat), around internal organs (visceral fat), in bone marrow (yellow bone marrow), intermuscular (Muscular system) and in the breast tissue. Adipose tissue is found in specific locations, which are referred to as adipose depots. Apart from adipocytes, which comprise the highest percentage of cells within adipose tissue, other cell types are present, collectively termed stromal vascular fraction (SVF) of cells. SVF includes preadipocytes, fibroblasts, adipose tissue macrophages, and endothelial cells. Adipose tissue contains many small blood vessels. In the integumentary system, which includes the skin, it accumulates in the deepest level, the subcutaneous layer, providing insulation from heat and cold. Around organs, it provides protective padding. However, its main function is to be a reserve of lipids, which can be burned to meet the energy needs of the body and to protect it from excess glucose by storing triglycerides produced by the liver from sugars, although some evidence suggests that most lipid synthesis from carbohydrates occurs in the adipose tissue itself.[4] Adipose depots in different parts of the body have different biochemical profiles. Under normal conditions, it provides feedback for hunger and diet to the brain.

Mice have eight major adipose depots, four of which are within the abdominal cavity.[1] The paired gonadal depots are attached to the uterus and ovaries in females and the epididymis and testes in males; the paired retroperitoneal depots are found along the dorsal wall of the abdomen, surrounding the kidney, and, when massive, extend into the pelvis. The mesenteric depot forms a glue-like web that supports the intestines and the omental depot (which originates near the stomach and spleen) and- when massive- extends into the ventral abdomen. Both the mesenteric and omental depots incorporate much lymphoid tissue as lymph nodes and milky spots, respectively. The two superficial depots are the paired inguinal depots, which are found anterior to the upper segment of the hind limbs (underneath the skin) and the subscapular depots, paired medial mixtures of brown adipose tissue adjacent to regions of white adipose tissue, which are found under the skin between the dorsal crests of the scapulae. The layer of brown adipose tissue in this depot is often covered by a "frosting" of white adipose tissue; sometimes these two types of fat (brown and white) are hard to distinguish. The inguinal depots enclose the inguinal group of lymph nodes. Minor depots include the pericardial, which surrounds the heart, and the paired popliteal depots, between the major muscles behind the knees, each containing one large lymph node.[5] Of all the depots in the mouse, the gonadal depots are the largest and the most easily dissected,[6] comprising about 30% of dissectible fat.[7]

In an obese person, excess adipose tissue hanging downward from the abdomen is referred to as a panniculus (or pannus). A panniculus complicates surgery of the morbidly obese individual. It may remain as a literal "apron of skin" if a severely obese person quickly loses large amounts of fat (a common result of gastric bypass surgery). This condition cannot be effectively corrected through diet and exercise alone, as the panniculus consists of adipocytes and other supporting cell types shrunken to their minimum volume and diameter.[citation needed] Reconstructive surgery is one method of treatment.

Visceral fat or abdominal fat[8] (also known as organ fat or intra-abdominal fat) is located inside the abdominal cavity, packed between the organs (stomach, liver, intestines, kidneys, etc.). Visceral fat is different from subcutaneous fat underneath the skin, and intramuscular fat interspersed in skeletal muscles. Fat in the lower body, as in thighs and buttocks, is subcutaneous and is not consistently spaced tissue, whereas fat in the abdomen is mostly visceral and semi-fluid.[9] Visceral fat is composed of several adipose depots, including mesenteric, epididymal white adipose tissue (EWAT), and perirenal depots. Visceral fat is often expressed in terms of its area in cm2 (VFA, visceral fat area).[10]

An excess of visceral fat is known as central obesity, or "belly fat", in which the abdomen protrudes excessively and new developments such as the Body Volume Index (BVI) are specifically designed to measure abdominal volume and abdominal fat. Excess visceral fat is also linked to type 2 diabetes,[11]insulin resistance,[12]inflammatory diseases,[13] and other obesity-related diseases.[14] Likewise, the accumulation of neck fat (or cervical adipose tissue) has been shown to be associated with mortality.[15]

Men are more likely to have fat stored in the abdomen due to sex hormone differences. Female sex hormone causes fat to be stored in the buttocks, thighs, and hips in women.[16][17] When women reach menopause and the estrogen produced by the ovaries declines, fat migrates from the buttocks, hips and thighs to the waist;[18] later fat is stored in the abdomen.[19]

High-intensity exercise is one way to effectively reduce total abdominal fat.[20][21] One study suggests at least 10 MET-hours per week of aerobic exercise is required for visceral fat reduction.[22]

Epicardial adipose tissue (EAT) is a particular form of visceral fat deposited around the heart and found to be a metabolically active organ that generates various bioactive molecules, which might significantly affect cardiac function.[23] Marked component differences have been observed in comparing EAT with subcutaneous fat, suggesting a depot specific impact of stored fatty acids on adipocyte function and metabolism.[24]

Most of the remaining nonvisceral fat is found just below the skin in a region called the hypodermis.[25] This subcutaneous fat is not related to many of the classic obesity-related pathologies, such as heart disease, cancer, and stroke, and some evidence even suggests it might be protective.[26] The typically female (or gynecoid) pattern of body fat distribution around the hips, thighs, and buttocks is subcutaneous fat, and therefore poses less of a health risk compared to visceral fat.[27]

Like all other fat organs, subcutaneous fat is an active part of the endocrine system, secreting the hormones leptin and resistin.[25]

The relationship between the subcutaneous adipose layer and total body fat in a person is often modelled by using regression equations. The most popular of these equations was formed by Durnin and Wormersley, who rigorously tested many types of skinfold, and, as a result, created two formulae to calculate the body density of both men and women. These equations present an inverse correlation between skinfolds and body densityas the sum of skinfolds increases, the body density decreases.[28]

Factors such as sex, age, population size or other variables may make the equations invalid and unusable, and, as of 2012[update], Durnin and Wormersley's equations remain only estimates of a person's true level of fatness. New formulae are still being created.[28]

Ectopic fat is the storage of triglycerides in tissues other than adipose tissue, that are supposed to contain only small amounts of fat, such as the liver, skeletal muscle, heart, and pancreas.[1] This can interfere with cellular functions and hence organ function and is associated with insulin resistance in type-2 diabetes.[29] It is stored in relatively high amounts around the organs of the abdominal cavity, but is not to be confused as visceral fat.

The specific cause for the accumulation of ectopic fat is unknown. The cause is likely a combination of genetic, environmental, and behavioral factors that are involved in excess energy intake and decreased physical activity. Substantial weight loss can reduce ectopic fat stores in all organs and this is associated with an improvement of the function of that organ.[29]

Free fatty acids are liberated from lipoproteins by lipoprotein lipase (LPL) and enter the adipocyte, where they are reassembled into triglycerides by esterifying it onto glycerol. Human fat tissue contains about 87% lipids[citation needed].

There is a constant flux of FFA (Free Fatty Acids) entering and leaving adipose tissue. The net direction of this flux is controlled by insulin and leptinif insulin is elevated, then there is a net inward flux of FFA, and only when insulin is low can FFA leave adipose tissue. Insulin secretion is stimulated by high blood sugar, which results from consuming carbohydrates.

In humans, lipolysis (hydrolysis of triglycerides into free fatty acids) is controlled through the balanced control of lipolytic B-adrenergic receptors and a2A-adrenergic receptor-mediated antilipolysis.

Fat cells have an important physiological role in maintaining triglyceride and free fatty acid levels, as well as determining insulin resistance. Abdominal fat has a different metabolic profilebeing more prone to induce insulin resistance. This explains to a large degree why central obesity is a marker of impaired glucose tolerance and is an independent risk factor for cardiovascular disease (even in the absence of diabetes mellitus and hypertension).[30] Studies of female monkeys at Wake Forest University (2009) discovered that individuals suffering from higher stress have higher levels of visceral fat in their bodies. This suggests a possible cause-and-effect link between the two, wherein stress promotes the accumulation of visceral fat, which in turn causes hormonal and metabolic changes that contribute to heart disease and other health problems.[31]

Recent advances in biotechnology have allowed for the harvesting of adult stem cells from adipose tissue, allowing stimulation of tissue regrowth using a patient's own cells. In addition, adipose-derived stem cells from both human and animals reportedly can be efficiently reprogrammed into induced pluripotent stem cells without the need for feeder cells.[32] The use of a patient's own cells reduces the chance of tissue rejection and avoids ethical issues associated with the use of human embryonic stem cells.[33] A growing body of evidence also suggests that different fat depots (i.e. abdominal, omental, pericardial) yield adipose-derived stem cells with different characteristics.[33][34] These depot-dependent features include proliferation rate, immunophenotype, differentiation potential, gene expression, as well as sensitivity to hypoxic culture conditions.[35]

Adipose tissue is the greatest peripheral source of aromatase in both males and females,[citation needed] contributing to the production of estradiol.

Adipose derived hormones include:

Adipose tissues also secrete a type of cytokines (cell-to-cell signalling proteins) called adipokines (adipocytokines), which play a role in obesity-associated complications. Perivascular adipose tissue releases adipokines such as adiponectin that affect the contractile function of the vessels that they surround.[1][36]

Brown fat or brown adipose tissue is a specialized form of adipose tissue in humans and other mammals.[37] It is located mainly around the neck and large blood vessels of the thorax. This specialized tissue can generate heat by "uncoupling" the respiratory chain of oxidative phosphorylation within mitochondria. The process of uncoupling means that when protons transit down the electrochemical gradient across the inner mitochondrial membrane, the energy from this process is released as heat rather than being used to generate ATP. This thermogenic process may be vital in neonates exposed to cold, which then require this thermogenesis to keep warm, as they are unable to shiver, or take other actions to keep themselves warm.[38]

Attempts to simulate this process pharmacologically have so far been unsuccessful. Techniques to manipulate the differentiation of "brown fat" could become a mechanism for weight loss therapy in the future, encouraging the growth of tissue with this specialized metabolism without inducing it in other organs.

Until recently, brown adipose tissue was thought to be primarily limited to infants in humans, but new evidence has now overturned that belief. Metabolically active tissue with temperature responses similar to brown adipose was first reported in the neck and trunk of some human adults in 2007,[39] and the presence of brown adipose in human adults was later verified histologically in the same anatomical regions.[40][41][42]

Browning of WAT, also referred to as beiging, occurs when adipocytes within WAT depots develop features of BAT. Beige adipocytes take on a multilocular appearance (containing several lipid droplets) and increase expression of uncoupling protein 1 (UCP1).[43] In doing so, these normally energy-storing adipocytes become energy-releasing adipocytes.

UCP1 is a protein predominantly found in BAT.[44] It acts to dissipate the proton gradient generated by oxidative phosphorylation, leading to the production of heat. Release of catecholamines from sympathetic nerves results in UCP1 activation and usually occurs after extended periods of cold exposure or in response to overfeeding.[45] UCP1 activity is stimulated by long chain fatty acids that are produced subsequent to -adrenergic receptor activation.[46] UCP1 is proposed to function as a fatty acid proton symporter, although the exact mechanism has yet to be elucidated.[47] In contrast, UCP1 is inhibited by ATP, ADP, and GTP.[48]

The calorie-burning capacity of brown and beige fat has been extensively studied as research efforts focus on therapies targeted to treat obesity and diabetes. The drug 2,4-dinitrophenol, which also acts as a chemical uncoupler similarly to UCP1, was used for weight loss in the 1930s. However, it was quickly discontinued when excessive dosing led to adverse side effects including hyperthermia and death.[43] 3 agonists, like CL316,243, have also been developed and tested in humans. However, the use of such drugs has proven largely unsuccessful due to several challenges, including varying species receptor specificity and poor oral bioavailability.[49]

Cold is a primary regulator of BAT processes and induces WAT browning. Browning in response to chronic cold exposure has been well documented and is a reversible process. A study in mice demonstrated that cold-induced browning can be completely reversed in 21 days, with measurable decreases in UCP1 seen within a 24 hour period.[50] A study by Rosenwald et al. revealed that when the animals are re-exposed to a cold environment, the same adipocytes will adopt a beige phenotype, suggesting that beige adipocytes are retained.[51]

Transcriptional regulators, as well as a growing number of other factors, regulate the induction of beige fat. Three regulators of transcription are central to WAT browning and serve as targets for many of the molecules known to influence this process.[52] These include peroxisome proliferator-activated receptor gamma (PPAR), PR domain containing 16 (PRDM16), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1).[52] The list of molecules that influence browning has grown in direct proportion to the popularity of this topic and is constantly evolving as more knowledge is acquired. Among these molecules are irisin and fibroblast growth factor 21 (FGF21), which have been well-studied and are believed to be important regulators of browning. Irisin is secreted from muscle in response to exercise and has been shown to increase browning by acting on beige preadipocytes.[53] FGF21, a hormone secreted mainly by the liver, has garnered a great deal of interest after being identified as a potent stimulator of glucose uptake and a browning regulator through its effects on PGC-1.[43] It is increased in BAT during cold exposure and is thought to aid in resistance to diet-induced obesity[54] FGF21 may also be secreted in response to exercise and a low protein diet, although the latter has not been thoroughly investigated.[55][56] Data from these studies suggest that environmental factors like diet and exercise may be important mediators of browning.

Due to the complex nature of adipose tissue and a growing list of browning regulatory molecules, great potential exists for the use of bioinformatics tools to improve study within this field. Studies of WAT browning have greatly benefited from advances in these techniques, as beige fat is rapidly gaining popularity as a therapeutic target for the treatment of obesity and diabetes.

DNA microarray is a bioinformatics tool used to quantify expression levels of various genes simultaneously, and has been used extensively in the study of adipose tissue. One such study used microarray analysis in conjunction with Ingenuity IPA software to look at changes in WAT and BAT gene expression when mice were exposed to temperatures of 28 and 6C.[57] The most significantly up- and downregulated genes were then identified and used for analysis of differentially expressed pathways. It was discovered that many of the pathways upregulated in WAT after cold exposure are also highly expressed in BAT, such as oxidative phosphorylation, fatty acid metabolism, and pyruvate metabolism.[57] This suggests that some of the adipocytes switched to a beige phenotype at 6C. Mssenbck et al. also used microarray analysis to demonstrate that insulin deficiency inhibits the differentiation of beige adipocytes but does not disturb their capacity for browning.[58] These two studies demonstrate the potential for the use of microarray in the study of WAT browning.

RNA sequencing (RNA-Seq) is a powerful computational tool that allows for the quantification of RNA expression for all genes within a sample. Incorporating RNA-Seq into browning studies is of great value, as it offers better specificity, sensitivity, and a more comprehensive overview of gene expression than other methods. RNA-Seq has been used in both human and mouse studies in an attempt characterize beige adipocytes according to their gene expression profiles and to identify potential therapeutic molecules that may induce the beige phenotype. One such study used RNA-Seq to compare gene expression profiles of WAT from wild-type (WT) mice and those overexpressing Early B-Cell Factor-2 (EBF2). WAT from the transgenic animals exhibited a brown fat gene program and had decreased WAT specific gene expression compared to the WT mice.[59] Thus, EBF2 has been identified as a potential therapeutic molecule to induce beiging.

Chromatin immunoprecipitation with sequencing (ChIP-seq) is a method used to identify protein binding sites on DNA and assess histone modifications. This tool has enabled examination of epigenetic regulation of browning and helps elucidate the mechanisms by which protein-DNA interactions stimulate the differentiation of beige adipocytes. Studies observing the chromatin landscapes of beige adipocytes have found that adipogenesis of these cells results from the formation of cell specific chromatin landscapes, which regulate the transcriptional program and, ultimately, control differentiation. Using ChIP-seq in conjunction with other tools, recent studies have identified over 30 transcriptional and epigenetic factors that influence beige adipocyte development.[59]

The thrifty gene hypothesis (also called the famine hypothesis) states that in some populations the body would be more efficient at retaining fat in times of plenty, thereby endowing greater resistance to starvation in times of food scarcity. This hypothesis, originally advanced in the context of glucose metabolism and insulin resistance, has been discredited by physical anthropologists, physiologists, and the original proponent of the idea himself with respect to that context, although according to its developer it remains "as viable as when [it was] first advanced" in other contexts.[60][61]

In 1995, Jeffrey Friedman, in his residency at the Rockefeller University, together with Rudolph Leibel, Douglas Coleman et al. discovered the protein leptin that the genetically obese mouse lacked.[62][63][64] Leptin is produced in the white adipose tissue and signals to the hypothalamus. When leptin levels drop, the body interprets this as a loss of energy, and hunger increases. Mice lacking this protein eat until they are four times their normal size.

Leptin, however, plays a different role in diet-induced obesity in rodents and humans. Because adipocytes produce leptin, leptin levels are elevated in the obese. However, hunger remains, and- when leptin levels drop due to weight loss- hunger increases. The drop of leptin is better viewed as a starvation signal than the rise of leptin as a satiety signal.[65] However, elevated leptin in obesity is known as leptin resistance. The changes that occur in the hypothalamus to result in leptin resistance in obesity are currently the focus of obesity research.[66]

Gene defects in the leptin gene (ob) are rare in human obesity.[67] As of July, 2010, only 14 individuals from five families have been identified worldwide who carry a mutated ob gene (one of which was the first ever identified cause of genetic obesity in humans)two families of Pakistani origin living in the UK, one family living in Turkey, one in Egypt, and one in Austria[68][69][70][71][72]and two other families have been found that carry a mutated ob receptor.[73][74] Others have been identified as genetically partially deficient in leptin, and, in these individuals, leptin levels on the low end of the normal range can predict obesity.[75]

Several mutations of genes involving the melanocortins (used in brain signaling associated with appetite) and their receptors have also been identified as causing obesity in a larger portion of the population than leptin mutations.[76]

In 2007, researchers isolated the adipose gene, which those researchers hypothesize serves to keep animals lean during times of plenty. In that study, increased adipose gene activity was associated with slimmer animals.[77] Although its discoverers dubbed this gene the adipose gene, it is not a gene responsible for creating adipose tissue.

Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes. Recent studies shed light into potential molecular mechanisms in the fate determination of pre-adipocytes although the exact lineage of adipocyte is still unclear.[78][79]

Adipose tissue has a density of ~0.9g/ml.[80] Thus, a person with more adipose tissue will float more easily than a person of the same weight with more muscular tissue, since muscular tissue has a density of 1.06g/ml.[81]

A body fat meter is a widely available tool used to measure the percentage of fat in the human body. Different meters use various methods to determine the body fat to weight ratio. They tend to under-read body fat percentage.[82]

In contrast with clinical tools, one relatively inexpensive type of body fat meter uses the principle of bioelectrical impedance analysis (BIA) in order to determine an individual's body fat percentage. To achieve this, the meter passes a small, harmless, electric current through the body and measures the resistance, then uses information on the person's weight, height, age, and sex to calculate an approximate value for the person's body fat percentage. The calculation measures the total volume of water in the body (lean tissue and muscle contain a higher percentage of water than fat), and estimates the percentage of fat based on this information. The result can fluctuate several percentage points depending on what has been eaten and how much water has been drunk before the analysis.

Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative Macrophage activation, and a propensity towards type 2 cytokine expression. Furthermore, this effect was exaggerated when the mice became obese from a high fat diet.[83]

Diagrammatic sectional view of the skin (magnified).

White adipose tissue in paraffin section

Electronic instrument of body fat meter

Original post:
Adipose tissue - Wikipedia

Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat.[1]

There are two types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT), which are also known as white fat and brown fat, respectively, and comprise two types of fat cells. Most recently, the presence of beige adipocytes with a gene expression pattern distinct from either white or brown adipocytes has been described.

White fat cells or monovacuolar cells contain a large lipid droplet surrounded by a layer of cytoplasm. The nucleus is flattened and located on the periphery. A typical fat cell is 0.1mm in diameter with some being twice that size and others half that size. The fat stored is in a semi-liquid state, and is composed primarily of triglycerides and cholesteryl ester. White fat cells secrete many proteins acting as adipokines such as resistin, adiponectin, leptin and apelin. An average human adult has 30 billion fat cells with a weight of 30lbs or 13.5kg. If excess weight is gained as an adult, fat cells increase in size about fourfold before dividing and increasing the absolute number of fat cells present.[2]

Brown fat cells or plurivacuolar cells are polygonal in shape. Unlike white fat cells, these cells have considerable cytoplasm, with lipid droplets scattered throughout. The nucleus is round, and, although eccentrically located, it is not in the periphery of the cell. The brown color comes from the large quantity of mitochondria. Brown fat, also known as "baby fat," is used to generate heat.

Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes. Recent studies shed light into potential molecular mechanisms in the fate determination of pre-adipocytes although the exact lineage of adipocyte is still unclear.[3][4] The variation of body fat distribution resulting from normal growth is influenced by nutritional and hormonal status in dependence on intrinsic differences in cells found in each adipose depot.[5]

Mesenchymal stem cells can differentiate into adipocytes, connective tissue, muscle or bone.[1]

The term "lipoblast" is used to describe the precursor of the adult cell. The term "lipoblastoma" is used to describe a tumor of this cell type.[6]

Even after marked weight loss, the body never loses adipocytes.[citation needed]As a rule, to facilitate changes in weight, the adipocytes in the body merely gain or lose fat content. However, if the adipocytes in the body reach their maximum capacity of fat, they may replicate to allow additional fat storage.

Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet[clarification needed] to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain.[7]

In some reports and textbooks, the number of adipocytes can increase in childhood and adolescence, though the amount is usually constant in adults. Interestingly, individuals who become obese as adults, rather than as adolescents, have no more adipocytes than they had before.[8]

People who have been fat since childhood generally have an inflated number of fat cells. People who become fat as adults may have no more fat cells than their lean peers, but their fat cells are larger. In general, people with an excess of fat cells find it harder to lose weight and keep it off than the obese who simply have enlarged fat cells.[9]

According to research by Tchoukalova et al., 2010, body fat cells could have regional responses to the overfeeding that was studied in adult subjects. In the upper body, an increase of adipocyte size correlated with upper-body fat gain; however, the number of fat cells was not significantly changed. In contrast to the upper body fat cell response, the number of lower-body adipocytes did significantly increase during the course of experiment. Notably, there was no change in the size of the lower-body adipocytes.[10]

Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index without a significant increase in the overall number of adipocytes in adulthood.[8]

Obesity is characterized by the expansion of fat mass, through adipocyte size increase (hypertrophy) and, to a lesser extent, cell proliferation (hyperplasia).[11] In the fat cells of obese individuals, there is increased production of metabolism modulators, such as glycerol, hormones, and pro-inflammatory cytokines, leading to the development of insulin resistance.[12]

Fat production in adipocytes is strongly stimulated by insulin. By controlling the activity of the pyruvate dehydrogenase and the acetyl-CoA carboxylase enzymes, insulin promotes unsaturated fatty acid synthesis. It also promotes glucose uptake and induces SREBF1, which activates the transcription of genes that stimulate lipogenesis.[13]

SREBF1 (sterol regulatory element-binding transcription factor 1) is a transcription factor synthesized as an inactive precursor protein inserted into the endoplasmic reticulum (ER) membrane by two membrane-spanning helices. Also anchored in the ER membrane is SCAP (SREBF-cleavage activating protein), which binds SREBF1. The SREBF1-SCAP complex is retained in the ER membrane by INSIG1 (insulin-induced gene 1 protein). When sterol levels are depleted, INSIG1 releases SCAP and the SREBF1-SCAP complex can be sorted into COPII-coated transport vesicles that are exported to the Golgi. In the Golgi, SREBF1 is cleaved and released as a transcriptionally active mature protein. It is then free to translocate to the nucleus and activate the expression of its target genes.

[14]

Clinical studies have repeatedly shown that even though insulin resistance is usually associated with obesity, the membrane phospholipids of the adipocytes of obese patients generally still show an increased degree of fatty acid unsaturation.[15] This seems to point to an adaptive mechanism that allows the adipocyte to maintain its functionality, despite the increased storage demands associated with obesity and insulin resistance.

A study conducted in 2013[15] found that, while INSIG1 and SREBF1 mRNA expression was decreased in the adipose tissue of obese mice and humans, the amount of active SREBF1 was increased in comparison with normal mice and non-obese patients. This downregulation of INSIG1 expression combined with the increase of mature SREBF1 was also correlated with the maintenance of SREBF1-target gene expression. Hence, it appears that, by downregulating INSIG1, there is a resetting of the INSIG1/SREBF1 loop, allowing for the maintenance of active SREBF1 levels. This seems to help compensate for the anti-lipogenic effects of insulin resistance and thus preserve adipocyte fat storage abilities and availability of appropriate levels of fatty acid unsaturation in face of the nutritional pressures of obesity.

Adipocytes can synthesize estrogens from androgens,[16] potentially being the reason why being underweight or overweight are risk factors for infertility.[17] Additionally, adipocytes are responsible for the production of the hormone leptin. Leptin is important in regulation of appetite and acts as a satiety factor.[18]

See more here:
Adipocyte - Wikipedia

Open Access

Article

The Arabidopsis CERK1associated kinase PBL27 connects chitin perception to MAPK activation

These authors contributed equally to this work as first authors

These authors contributed equally to this work as third authors

Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1associated kinase PBL27, providing a missing link between pathogen perception and signaling output.

Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1associated kinase PBL27, providing a missing link between pathogen perception and signaling output.

CERK1associated kinase PBL27 interacts with MAPKKK5 at the plasma membrane.

Chitin perception induces disassociation of PBL27 and MAPKKK5.

PBL27 functions as a MAPKKK kinase.

Phosphorylation of MAPKKK5 by PBL27 is enhanced upon phosphorylation of PBL27 by CERK1.

Phosphorylation of MAPKKK5 by PBL27 is required for chitininduced MAPK activation in planta.

Kenta Yamada, Koji Yamaguchi, Tomomi Shirakawa, Hirofumi Nakagami, Akira Mine, Kazuya Ishikawa, Masayuki Fujiwara, Mari Narusaka, Yoshihiro Narusaka, Kazuya Ichimura, Yuka Kobayashi, Hidenori Matsui, Yuko Nomura, Mika Nomoto, Yasuomi Tada, Yoichiro Fukao, Tamo Fukamizo, Kenichi Tsuda, Ken Shirasu, Naoto Shibuya, Tsutomu Kawasaki

See the rest here:
Home | The EMBO Journal

more than 60 diseases can be treated with stem cells Read More...

Patient from Portugal, Diagnosed Multiple Sclerosis, One month after treatment he could walk again Read More...

Swiss Medica participated in neuro rehabilitation conference march 2015Read More...

NEW modern technology - activating autologous stem cells and replacing damaged cells

Patient from Portugal, 44 years old. Diagnosed Multiple Sclerosis.

In December 2012 his condition exacerbated. He started using wheelchairs. His disease progressed. He was not able to walk. He was not able to see. Nine months of usual treatments for MS accompanied by chemotherapy did not help. Then he found Swiss Medica Stem Cell Clinic. Stem celltreatment started immediately. One month later he was able to walk again.

SEE WHOLE STORY ABOUT J PAUL >>>

Holistic medicine considers a person to be a functional unit. The disease symptoms are signs of disruption in the system of the body. By activating the bodys ability of self-regulation we can eliminate this disruption. In Swiss Medica XXI Century S.A. we seek the cause of the disease, and provide a setting: to allow the body to use its own powers of self-healing to overcome the disease.

Our primary task is to make your own cells treat your own body. We use advanced technology to activate dormant cells (adipose mesenchymal stem cells) to differentiate into the cells we need, and then to replace the damaged cells. Symptoms become less prominent and disappear.

All form fields are required.

Read this article:
Stem cells treatment clinic

As part of a facial fat transfer procedure, physicians are now able incorporate stem cells to help patients achieve the best possible results. Traditional facial fat transfer procedures involve using the patients own body fat to plump up sunken or emaciated areas of the face but the results dont usually last very long. Adult stem cells can be introduced to the process to improve long-term results. Stem cell facial fat transfer procedures are used to treat chronic skin conditions like wrinkles, sun damage and redness.

Stem cells are being used in facial fat transfer procedures because they help stimulate fat cells, which die as we age. When fat cells die, they often cause areas of the face to look sunken, which can cause wrinkles and sagging skin. Stem cells are also believed to encourage cell regeneration, which repairs cells damaged by the sun and aging. Stem cells also stimulate skin cells to produce more collagen and elastin, which thicken and firm skin. Stem cell facial fat transfer procedures are a noninvasive way for patients to reduce natural signs of aging in a natural way.

Adult stem cells are used during fat transfer procedures. These stem cells are different from embryonic stem cells because they are autologous meaning they are extracted from fat in the patients abdomen or thigh. During facial fat transfer procedures, the fat removal and stem cell removal is accomplished at the same time.

Adult stem cells are naturally occurring and regenerative, so the patient is not affected by the removal. Stem cells can be found in various tissues throughout the body and are often referred to as undifferentiated cells meaning they are essentially a biological blank slate. Because of this, stem cells are capable of becoming another differentiated type of cell such as a skin cell, a fat cell or a muscle cell. Stem cells are added to facial fat transfer procedures to improve the quality, health and appearance of the skin over the long term.

A stem cell fat transfer procedure is accomplished in less than an hour, and the patient is given a local anesthetic no general or intravenous anesthesia is necessary. The physician will start by removing the subcutaneous fat from the abdomen or thigh area using a small syringe. Once its harvested, the physician will separate the fat cells, stem cells and growth factor from the fat. This mixture will later be re-injected into the treatment area.

What makes stem cell facial fat transfer procedures different from other fat transfer procedures is that the fat cells and stem cells are mixed with specific combination of growth factors that help them survive. Autologous growth factors such as platelet-rich plasma (PRP) are embedded in micro-hydraulic acid beads to allow for the release of these growth factors over longer periods of time. By constantly stimulating the fat cells and stem cells, growth factors help the damaged tissues develop into healthy tissue.

This anti-aging process ultimately restores lost fat, enhances the volume of the face, and improves the quality and texture of the skin. The procedure usually involves up to three injections of this mixture so that each layer of the skin receives even treatment.

Each patients recovery from a stem cell facial fat transfer procedure will be different depending on the condition being treated. Its important to note that it is not just the face that needs to heal, but the donor site as well. Following the procedure, patients may experience some swelling and bruising around the treatment area during the first seven to 10 days. During this time, patients want to avoid movement in the treatment area to avoid damage to the graft. Minor soreness is expected within the first couple days at the donor site, but it is usually manageable with over-the-counter pain medications.

The effects of this procedure typically last for five to six years. However, with regular care and follow-up appointments to reintroduce growth factors as a way to increase tissue survival, results can last up to eight to 10 years. Results develop over time and are seen during the course of three to four months. Patients have been thrilled with their results because their skin looks and feels better.

Request more information about stem cell facial fat transfer today. Call (317) 900-4440 or contact Dr. Michele Zormeier online.

Read more here:
Stem Cell Facial Fat Transfer in Zionsville, IN

Adipose tissue is an inexhaustible source of adult fat stem cells.

Have been identified stem cells capable of producing fat tissue. These fat stem cells from adipose tissue may help to understand how it develops fat tissue and which drugs or develop treatments against obesity. There are two types of adipose tissue: the white adipose tissue (WAT) and brown adipose tissue (BAT), the first one lipid rich while the second one lipids burning and warm producing. BAT founds in adult humans and it is very important to research on obesity because it represents a potential pathway by which the body controls the metabolism burning excess fat to produce heat. Adipose stem cells have many therapeutic Aplications: repair and regeneration of damaged tissues. Can be recovered in large quantities through liposuction or fragments of subcutaneous adipose tissue and can be easily expanded in vitro.

Stem cells have the unique characteristic of being able to choose, with each cell division, whether to produce copies of themselves or specialized cell. Thanks to this characteristic, the stem cells are critical for the maintenance of tissues such as blood, skin and intestines.

The regeneration represents a real alternative: expect the body to repair the damage inflicted by disease, accidents or aging through its stem cells.

Original post:
Fat Stem Cells Doc. Alberto Rossi Todde

Abstract

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) that possess many of the same regenerative properties as other MSCs. However, the ubiquitous presence of ADSCs and their ease of access in human tissue have led to a burgeoning field of research. The plastic surgeon is uniquely positioned to harness this technology because of the relative frequency in which they perform procedures such as liposuction and autologous fat grafting. This review examines the current landscape of ADSC isolation and identification, summarizes the current applications of ADSCs in the field of plastic surgery, discusses the risks associated with their use, current barriers to universal clinical translatability, and surveys the latest research which may help to overcome these obstacles.

Recent advances in regenerative medicine, in particular the discovery of multipotent, easily accessible stem cells such as adipose-derived stem cells (ADSCs), have provided the opportunity of using autologous stem cell transplants as regenerative therapies. The field of plastic surgery, centred on the restoration and enhancement of the body, is logically positioned to utilize such new technologies focused on the repair and replacement of diseased cells and tissues [1]. The ability of stem cells to self-renew, to secrete trophic factors and to differentiate into different cell types has allowed for the development of more flexible therapies to redefine the classic autologous tissue transplant and offer more customizable treatment options. ADSCs are being utilized for a variety of different applications in plastic surgery [2-11], and as our understanding of the basic science of stem cells continues to develop, the plastic surgeon should be prepared for the translational and clinical implications of this progress.

Adipose-derived stem cells are particularly useful as they can be easily harvested with minimal donor site morbidity and have a differentiation potential similar to other MSCs [12, 13]. In addition, ADSCs have higher yields and greater proliferative rates in culture when compared to bone marrow stromal cells [14-16]. The discovery that ADSCs are not only precursors to adipocytes but also are multipotent progenitors to a variety of cells [17] including osteoblasts, chondrocytes, myocytes, epithelial cells and neuronal cells [18], creates the potential to treat a variety of tissue defects from a single, easily accessible autologous cell source.

Adult stem cell research has made significant strides as a therapeutic modality in recent years. However, there remain significant barriers to the safe and efficacious use of stem cell therapies. With regard to ADSCs, this includes better defining the source population of multipotent cells, optimizing the isolation of these cells in compliance with regulatory standards, and better understanding the behaviour of ADSCs in their transplanted niche. The purpose of this review is to (i) explore the utilization of ADSCs in plastic surgery, (ii) describe the current limitations of ADSC treatments with regard to developing translatable clinical therapies and (iii) describe certain techniques used in our laboratory that may help overcome these barriers. Understanding the current status of clinical ADSC treatments and defining the challenges ahead may bring us closer to achieving desired outcome while minimizing unwanted side effects with these therapies.

The most commonly published method of ADSC isolation involves enzymatic digestion of lipoaspirate to release the stromal vascular fraction (SVF) of cells which include stromal & endothelial cells, pericytes, various white blood cells, red blood cells and stem/progenitor cells [19]. The enzyme preparations used to achieve this fraction include dispase, trypsin and more commonly collagenase. In our laboratory, we take freshly harvested lipoaspirate and wash it with sterile 1% PBS until golden in colour. The adipose tissue is then digested with 0.01% collagenase/PBS solution at a ratio of 1ml of enzyme solution to 1cm3 of adipose tissue. This mixture is incubated at 37C with intermittent agitation until it becomes cloudy (usually 30min.). The infranatant is then carefully aspirated, transferred to 50ml conical tubes and centrifuged at 706g for 8min. The supernatant is discarded and resulting pellet, the SVF, is resuspended in control media [DMEM supplemented with 10% foetal bovine serum (FBS), 500IU penicillin and 500g streptomycin; Mediatech, Manassas, VA, USA]. The cells are then counted and plated in uncoated T75 flasks at a concentration of 1106 cells. Consistently, 20mg of lipoaspirate is ample tissue to harvest an adequate yield of SVF (>1107 cells).

In 2006, the International Society for Cellular Therapy (ICTS) defined a set of minimal criteria for identifying cells as ADSCs. These include plastic adherence while maintained in standard culture conditions, expression of CD73, CD90 and CD105 while lacking the expression of CD45, CD34, CD14 or CD11b, CD79 or CD19 and HLA-DR surface molecules [20]. In conjunction with the International Federation for Adipose Therapeutics and Science in 2013, the ICTS has denoted additional surface markers CD13, CD29 and CD44 as being constitutively expressed at >80% on the surface of ADSCs, while CD31, CD45 and CD235a are the primary negative markers that should be expressed on less than 2% of the cells [19]. Ultimately, the viability of the isolated cells should exceed 70% and the presence of at least two positive and two negative markers are necessary for foundational phenotyping. Finally, ADSCs must possess the ability to differentiate into osteoblasts, adipocytes and chondroblasts.

Identification of ADSCs in our laboratory is accomplished by labelling our plastic-adherent cells with a mesenchymal stem cell (MSC) phenotyping kit after the second passage (Miltenyi Biotec Inc, Auburn, CA, USA). Cells are analysed using a C6 Accuri Flow Cytometer (BD Biosciences, San Jose, CA, USA) which demonstrate positive staining for CD90 (81.3%), CD105 (86.6%) and CD73 (99.9%) and negative staining for CD14, CD20, CD34 and CD45 (1.97% Fig.1). To complete the identification of our ADSCs, we culture these cells in adipogenic, osteogenic, or chondrogenic conditions provided in commercially available kits (Cyagen Biosciences Inc., Sunnyvale, CA, USA). Cells subjected to adipogenic or osteogenic conditions reveal lipid droplets or calcium synthesis after staining with Oil Red O or Alizarin Red S, respectively, after fixation in 4% formalin. Cells subjected to chondrogenic conditions reveal proteoglycan synthesis upon staining with Alcian Blue after paraffin embedding (Fig.2). The ease at which ADSCs can be isolated has led to rapid and widespread translational applications.

Figure1. Flow cytometry analysis of isolated ADSCs after collagenase method. Cells stained (A) 81.3% positive for CD90, (B) 99.9% positive for CD73, (C) 86.6% positive for CD105 and (D) 1.97% positive for CD14, CD20, CD34 and CD45.

Download figure to PowerPoint

Figure2. Undifferentated and differentiated ADSCs visualized using microscopy. Original magnification, 10. (A) Control stain uADSCs stained with Oil Red O (other controls not shown). (B) Staining with Alcian Blue revealing presence of chondroblasts. (C) Staining with Oil Red O revealing presence of adipocytes. (D) Staining with Alizarin Red S revealing presence of osteoblasts.

Download figure to PowerPoint

A number of groups have described the isolation of ADSCs using non-enzymatic methods. Studies show that ADSCs reside in the infranatant layer of the suction canister after liposuction and that these cells can be expanded ex vivo. And while these cells exhibit phenotypic and differentiation potential similar to ADSCs isolated via collagenase digestion, their presence is significantly lower with reported yields ranging from a 3- to 19-fold decrease in comparison [21-24]. Interestingly, it has been found that multiple variables, including medical comorbidities of the patient, location adipose tissue stores, and the method in which this tissue is harvested, all affect the properties of the ADSCs therein. For example, diabetic patient fat stores have been found to contain fewer ADSCs with a reduced phenotypic expression profile and ability to proliferate [3]. The anatomical location of adipose tissue harvest also appears to have an effect on the yield and characteristics of the isolated ADSCs [25, 26]. More recently, Gnanasegaran etal. demonstrated that the gene expression levels and tendency towards specific germ layer differentiation is affected by whether the fat is harvested via liposuction versus lipectomy [27].

In Europe, ADSCs are considered Advanced Therapy Medicinal Products, as defined by the European Union (European Commission) 1394/2007 which contains rules for authorization, supervision, and pharmacovigilance regarding the summary of product characteristics, labelling, and packaging of Advanced Therapy Medicinal Products that are prepared commercially and in academic institutions [68]. This regulation refers to the European good manufacturing process (eGMP) rules [69]. The process of converting protocols, including collagenase-processed ADSCs, into a process that is compliant with eGMP requires assays that have had careful consideration of all the risks and benefits for the patient end user. As a result, the general recommendation on the use of enzyme-processed CAL in the clinical setting is not prohibited as this technique has been demonstrated to provide satisfying results in terms of long-term outcome, most likely because of the dramatic release of angiogenic growth factors and the differentiation of ADSCs into adipocytes and vascular endothelial cells [5, 10, 11].

In the United States, the Food and Drug Administration (FDA) regulates Human Cells and Tissue-Based Products (HCT/P) intended for human transplant and maintains two levels of classifications: 361 and 351 products. HCT/P 361 encompasses tissue (e.g. bone, ligaments, vein grafts, etc.) and their related procedures that take place in the same operative session, all of which fall under the jurisdiction of practice of medicine which is governed by state medical boards and professional societies; not the FDA. HCT/P 351, on the other hand, includes drugs/biologics (e.g. cultured cells, lymphocyte immune therapy, cell therapy involving the transfer of genetic material, etc.) which is fully governed by FDA [70, 71]. Regulation 21 CFR 1271 directly demonstrates the FDA's position on enzymatically isolated adipose stem cells derived from SVF for reconstructive purposes as beyond the scope of minimal manipulation and therefore, a drug [72]. Thus, the practical implication is the need for any surgeon who wishes to use ADSCs isolated via collagenase to submit an Investigational New Drug application to the FDA and have an approved Institutional Review Board with the referring Institution.

Given the time, expense and complexity of the regulatory issues surrounding ADSCs intended for transplantation, it is evident that U.S. physicians are discouraged to perform any cell-supplemented lipotransfer techniques in the current commonly accepted practices. Furthermore, automated devices for separating adipose stem cells are regulated as class III medical devices by the FDA, and currently, none are approved for human use in the United States. Kolle etal. demonstrated that CAL, when supplemented with ADSCs expanded ex vivo after collagenase digestion, yields superior results when compared to lipotransfer alone [38]. The FDA restrictions that would preclude such a study to be conducted in the United States prompt an impetus to develop methods for CAL that results in minimal manipulation of source adipose tissue.

In 2006, Yoshimura etal. described a cell population in the liposuction aspirate fluid that exhibited similar phenotypic properties to ADSCs harvested in the traditional manner (collagenase) from processed lipoaspirate cells; however, the yield was reduced by athird when comparing to the two methods [23]. Since that time, additional studies have been published touting the benefits of non-enzymatic ADSC isolation. In 2010, Francis etal. described a method of ADSC Rapid Isolation in ~30min. that excluded the use of collagenase, however, a significant disadvantage of this study was the low yield of ~250,000 cells from a starting volume of ~250ml liposuction aspirate fluid [21]. Zeng etal. describe a rapid and efficient form of non-enzymatic ADSC isolation in which adipose tissue is cut into tiny pieces and placed in culture flasks with 100% FBS in which the plastic-adherent cells were allowed to expand over a period of days [24]. One obvious downside to this method is the requirement to expand the cell population in calf serum. Most recently, Shah etal. describe aform of non-enzymatic ADSC isolation combining the cells of the liposuction aspirate fluid with the cells captured from the processed lipoaspirate tissue wash that is typically discarded prior to collagenase digestion [22]. They observed significant improvement in MSC-related phenotypic markers and similar adipogenic and osteogenic differentiation characteristics. While their isolation time was cut by one-third, they observed a 19-fold decrease in ADSC isolation when compared to the traditional method. In our laboratory, we have adopted a very similar protocol of non-enzymatic isolation that includes processing the processed lipoaspirate effluent. The primary difference in our protocol, however, is the method of plating cells. While Shah etal. plate the entire SVF pellets in T175 flasks, we resuspend our pellets in culture media and then plate the cells at specific concentrations. In one experiment for example, we plated the SVF pellet after collagenase digestion at a concentration of 5105 in a T75 flask. Concurrently, we plated the SVF pellet obtained after non-enzymatic isolation at 2106. After 6days of culture, these two flasks appeared nearly identical in terms of confluence, correlating to a fourfold decrease in ADSC harvest when using the latter method. The two cell populations were then analysed under flow cytometry as previously described. There is little difference in the phenotypic expression between the two populations as demonstrated by >80% expression of CD90, CD73 and CD105 and <5% expression of CD14, CD20, CD 34 and CD45 (Fig.3).

Figure3. Flow cytometry analysis of isolated ADSCs after rapid isolation (no collagenase). Cells stained (A) 85.8% positive for CD90, (B) 99.9% positive for CD73, (C) 99.4% positive for CD105 and (D) 3.79% positive for CD14, CD20, CD34 and CD45. (E) Collagenase-isolated ADSCs after 6days of primary culture seeded at 5105 in T75 flask. (F) Rapid isolation ADSCs after 6days primary culture seeded at 2106 in T75 flask.

Download figure to PowerPoint

Most convincingly, Kolle etal. demonstrated a clear benefit to CAL over lipotransfer alone. They isolated and expanded ADSCs ex vivo from human cases followed by lipotransfer to the cases arms with or without ADSC supplementation. They demonstrated a 65% improvement in fat graft survival after 4months in the experimental group [38]. The major drawback to their experimental model was that to achieve these results, the 34ml of lipotransfer was supplemented with 6.5108 ADSCs or 2000 times the physiological level [38]. The methods of rapid isolation, previously mentioned, demonstrate the ability to isolate ADSCs without the aid of enzymatic digestion, but at a cost of greatly reduced yields. There is significant doubt that ADSCs used at such low concentrations would serve for any clinical benefit. As previously discussed, ex vivo expansion of ADSCs is not practical for application in the United States or other principalities with strict regulations. Therein lies an impetus to discover innovative methods of ADSC isolation and characterization of the regenerative components of the SVF that might yield similar results to concentrated ADSCs alone.

There is promise in capitalizing on the plastic-adherent properties of ADSCs as a form of non-enzymatic isolation. The same group that first described the isolation of cells from the LAF, Doi etal., has demonstrated that an adherent column of rayonpolyethylene non-woven fabrics may also be used to isolate ADSCs, though at an inferior yield to the traditional method [73]. Further advancements in harnessing the plastic-adherent properties of these cells are clearly needed as Buschmann etal. demonstrated that 3050% of ADSCs remain in suspension after 24hrs of primary culture [74].

Go here to see the original:
Implications for human adipose-derived stem cells in ...

Fat vs. Bone Marrow Stem Cells: A Clinicians Perspective

This week I treated a patient with adipose SVF stem cells to augment a low stem cell yield from bone marrow. I dont do this often, as the quality of fat stem cells for orthopedic applications like arthritis is much less. We do use fat for an occasional structural graft in various procedures. Today I wanted to give you a clinicians eye view of the harvest procedures for both stem cell types that you wont see elsewhere, so let Fat vs Bone Marrow Stem Cells begin.

In summary, harvesting fat in a mini-liposuction is a violent affair, harvesting stem cells from a bone marrow aspirate is like an advanced blood draw. Let me explain.

In order to get fat through a mini-liposuction you need to first use a scalpel to open a small incision in the skin. This isnt at all required for a bone marrow aspiration as the needle is just inserted into the skin like any other needle. In the liposuction, the whole goal is disrupting large amounts of normal tissue. In fact, the stem cells live around the blood vessels, so you have to chew up as many blood vessels in the fat as possible to get a good stem cell yield. This involves placing a small wand like device under the skin and into the fat and moving it back and forth (through much resistance) to break apart large sections of tissue. The bone marrow aspiration simply involves directing the needle under the x-ray to the desired area of bone. The needle is then turned back and forth a few times to enter the bone (which is like hard plastic instead of cement). At this point in the liposuction the doctor must continue to break up large swaths of tissue with suction, sucking the broken tissue and blood vessels into a syringe. On the other hand, in the bone marrow aspiration the doctor simply draws the bone marrow aspirate (which looks like blood) into the syringe like a common blood draw.

The complication rates for these two procedures tell the rest of the story. Mini-liposuction procedures have surgical style complication rates of 3-10%, while bone marrow aspiration complication rates are so rare that only a handful occurred in more than 20,000 procedures in one U.K. registry. The upshot? It always makes me chuckle (in a bad way) when I hear fat stem cell advocates claim that a bone marrow aspiration procedure is so invasive. Youhavent seen invasive until youve seen a lipo-suction!

Disclaimer: Like all medical procedures, Regenexx Procedures have a success & failure rate. Not all patients will experience the same results.

If you liked this post, you may really enjoy this book by the same author - Dr. Chris Centeno

Written by Regenexx Founder, Dr. Chris Centeno, this 150 page book explains the Regenexx approach to patients and orthopedic conditions. Whether youre are an existing patient or simply interested in the human body and how everything in the body ties together, you will enjoy exploring this book in-depth. With hyperlinks to more detailed information, related studies and commentary, this book condenses a huge amount of data and resources into an enjoyable and entertaining read.

Chris Centeno, M.D. is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. Centeno regularly lectures on regenerative medicine and has spoken twice at the Vatican Stem Cell Conference.

Read the original:
Fat vs. Bone Marrow Stem Cells: A Clinicians Perspective

Chowing down on a high-fat diet may not only grow your waistline. It may also plump stem cell populations in your gutcells that are prone to producing tumors.

After about a year of feeding mice a diet of 60 percent fat, researchers found that the rodents had an unusually hefty population of cancer-susceptible intestinal stem cells and cells that act like stem cells. Those cells were supercharged by a protein called PPAR-, which can be switched on by the presence of fatty acids in the gut, the researchers reported.

The findings, published in Nature, may explain why epidemiological data in humans has repeatedly linked obesity to boosted risks of cancer, particularly colon cancer. It may also offer researchers a new target for knocking back the risks of cancer in the obese.

In the gut, there is usually a tiny pocket of stem cells that works to replenish the cells that line the intestine. These cells hang around for a lifetime, giving them extra opportunities to acquire mutations that could spur tumors.

In the fat-fed mice, which grew chubby, this tiny stem cell population unexpectedly flourished. And, progenitor cellsspecialized progeny of stem cellsstarted acting more like their parents, too. They lived longer, upping their opportunities to acquire mutations and tumor-spawning potential.

The researchers found that PPAR- was behind that boom in stem and progenitor cells. In petri-dish experiments, the researchers found that fatty acids from the high-fat diet increased the amounts of PPAR- cells were making.

That makes sense because the protein is known to switch on metabolic machinery that helps burn fat over carbohydrates. But the protein also seems to spark specific genetic changes that ignite the two cell populations, the researchers suggest.

In their fat mice, the researchers noted higher rates of spontaneous tumors than in control mice.

Still, the researchers will need to do more work to know if PPAR- and the stem cells explain the link between cancer and obesity in humans.

Nature, 2015. DOI: 10.1038/nature.2016.19484 (About DOIs).

See the original post:
High-fat diets may spur cancer by activating tumor-prone ...

What are Stem Cells?

Types of Stem Cells

Why are Stem Cells Important?

Can doctors use stem cells to treat patients?

Pros and Cons of Using Stem Cells

What are Stem Cells?

There are several different types of stem cells produced and maintained in our system throughout life. Depending on the circumstances and life cycle stages, these cells have different properties and functions. There are even stem cells that have been created in the laboratory that can help us learn more about how stem cells differentiate and function. A few key things to remember about stem cells before we venture into more detail:

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut.

Source ISSCR

Stem Cell History

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell is now known as induced pluripotent stem cells (iPSCs).

Source NIH

Types of Stem Cells

Adult Stem Cells (ASCs):

ASCs are undifferentiated cells found living within specific differentiated tissues in our bodies that can renew themselves or generate new cells that can replenish dead or damaged tissue. You may also see the term somatic stem cell used to refer to adult stem cells. The term somatic refers to non-reproductive cells in the body (eggs or sperm). ASCs are typically scarce in native tissues which have rendered them difficult to study and extract for research purposes.

Resident in most tissues of the human body, discrete populations of ASCs generate cells to replace those that are lost through normal repair, disease, or injury. ASCs are found throughout ones lifetime in tissues such as the umbilical cord, placenta, bone marrow, muscle, brain, fat tissue, skin, gut, etc. The first ASCs were extracted and used for blood production in 1948. This procedure was expanded in 1968 when the first adult bone marrow cells were used in clinical therapies for blood disease.

Studies proving the specificity of developing ASCs are controversial; some showing that ASCs can only generate the cell types of their resident tissue whereas others have shown that ASCs may be able to generate other tissue types than those they reside in. More studies are necessary to confirm the dispute.

Types of Adult Stem Cells

Embryonic Stem Cells (ESCs):

During days 3-5 following fertilization and prior to implantation, the embryo (at this stage, called a blastocyst), contains an inner cell mass that is capable of generating all the specialized tissues that make up the human body. ESCs are derived from the inner cell mass of an embryo that has been fertilized in vitro and donated for research purposes following informed consent. ESCs are not derived from eggs fertilized in a womans body.

These pluripotent stem cells have the potential to become almost any cell type and are only found during the first stages of development. Scientists hope to understand how these cells differentiate during development. As we begin to understand these developmental processes we may be able to apply them to stem cells grown in vitro and potentially regrow cells such as nerve, skin, intestine, liver, etc for transplantation.

Induced Pluripotent Stem Cells (iPSCs)

Induced pluripotent stem cells are stem cells that are created in the laboratory, a happy medium between adult stem cells and embryonic stem cells. iPSCs are created through the introduction of embryonic genes into a somatic cell (a skin cell for example) that cause it to revert back to a stem cell like state. These cells, like ESCs are considered pluripotent Discovered in 2007, this method of genetic reprogramming to create embryonic like cells, is novel and needs many more years of research before use in clinical therapies.

NIH

Why are Stem Cells Important?

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

Source NIH

Can doctors use stem cells to treat patients?

Some stem cells, such as the adult bone marrow or peripheral blood stem cells, have been used in clinical therapies for over 40 years. Other therapies utilizing stem cells include skin replacement from adult stem cells harvested from hair follicles that have been grown in culture to produce skin grafts. Other clinical trials for neuronal damage/disease have also been conducted using neural stem cells. There were side effects accompanying these studies and further investigation is warranted. Although there is much research to be conducted in the future, these studies give us hope for the future of therapeutics with stem cell research.

Potential Therapies using Stem Cells

Adult Stem Cell Therapies

Bone marrow and peripheral blood stem cell transplants have been utilized for over 40 years as therapy for blood disorders such as leukemia and lymphoma, amongst many others. Scientists have also shown that stem cells reside in most tissues of the body and research continues to learn how to identify, extract, and proliferate these cells for further use in therapy. Scientists hope to yield therapies for diseases such as type I diabetes and repair of heart muscle following heart attack.

Scientists have also shown that there is potential in reprogramming ASCs to cause them to transdifferentiate (turn back into a different cell type than the resident tissue it was replenishing).

Embryonic Stem Cell (ESC) Therapies

There is potential with ESCs to treat certain diseases in the future. Scientists continue to learn how ESCs differentiate and once this method is better understood, the hope is to apply the knowledge to get ESCs to differentiate into the cell of choice that is needed for patient therapy. Diseases that are being targeted with ESC therapy include diabetes, spinal cord injury, muscular dystrophy, heart disease, and vision/hearing loss.

Induced Pluripotent Stem Cell Therapies

Therapies using iPSCs are exciting because somatic cells of the recipient can be reprogrammed to en ESC like state. Then mechanisms to differentiate these cells may be applied to generate the cells in need. This is appealing to clinicians because this avoids the issue of histocompatibility and lifelong immunosuppression, which is needed if transplants use donor stem cells.

iPS cells mimic most ESC properties in that they are pluripotent cells, but do not currently carry the ethical baggage of ESC research and use because iPS cells have not been able to be manipulated to grow the outer layer of an embryonic cell required for the development of the cell into a human being.

Pros and Cons of Using Various Stem Cells

See the original post:
What are Stem Cells? - University of Nebraska Medical Center

An adult stem cell is thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ. The adult stem cell can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin (cells from the preimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.

Research on adult stem cells has generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for more than 40 years. Scientists now have evidence that stem cells exist in the brain and the heart, two locations where adult stem cells were not at firstexpected to reside. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies.

The history of research on adult stem cells began more than 60 years ago. In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some), were discovered a few years later. These non-hematopoietic stem cells make up a small proportion of the stromal cell population in the bone marrow and can generate bone, cartilage, and fat cells that support the formation of blood and fibrous connective tissue.

In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell typesastrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.

Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche"). In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.

Typically, there is a very small number of stem cells in each tissue and, once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells difficult. Scientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells in cell culture and to manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing insulin-producing cells for type1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.

Scientists often use one or more of the following methods to identify adult stem cells: (1) label the cells in a living tissue with molecular markers and then determine the specialized cell types they generate; (2) remove the cells from a living animal, label them in cell culture, and transplant them back into another animal to determine whether the cells replace (or "repopulate") their tissue of origin.

Importantly, scientists must demonstrate that a single adult stem cell can generate a line of genetically identical cells that then gives rise to all the appropriate differentiated cell types of the tissue. To confirm experimentally that a putative adult stem cell is indeed a stem cell, scientists tend to show either that the cell can give rise to these genetically identical cells in culture, and/or that a purified population of these candidate stem cells can repopulate or reform the tissue after transplant into an animal.

As indicated above, scientists have reported that adult stem cells occur in many tissues and that they enter normal differentiation pathways to form the specialized cell types of the tissue in which they reside.

Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells are available to divide for a long period, when needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of a particular tissue. The following are examples of differentiation pathways of adult stem cells (Figure 2) that have been demonstrated in vitro or in vivo.

Figure 2. Hematopoietic and stromal stem cell differentiation. Click here for larger image. ( 2008 Terese Winslow)

Transdifferentiation. A number of experiments have reported that certain adult stem cell types can differentiate into cell types seen in organs or tissues other than those expected from the cells' predicted lineage (i.e., brain stem cells that differentiate into blood cells or blood-forming cells that differentiate into cardiac muscle cells, and so forth). This reported phenomenon is called transdifferentiation.

Although isolated instances of transdifferentiation have been observed in some vertebrate species, whether this phenomenon actually occurs in humans is under debate by the scientific community. Instead of transdifferentiation, the observed instances may involve fusion of a donor cell with a recipient cell. Another possibility is that transplanted stem cells are secreting factors that encourage the recipient's own stem cells to begin the repair process. Even when transdifferentiation has been detected, only a very small percentage of cells undergo the process.

In a variation of transdifferentiation experiments, scientists have recently demonstrated that certain adult cell types can be "reprogrammed" into other cell types in vivo using a well-controlled process of genetic modification (see Section VI for a discussion of the principles of reprogramming). This strategy may offer a way to reprogram available cells into other cell types that have been lost or damaged due to disease. For example, one recent experiment shows how pancreatic beta cells, the insulin-producing cells that are lost or damaged in diabetes, could possibly be created by reprogramming other pancreatic cells. By "re-starting" expression of three critical beta cell genes in differentiated adult pancreatic exocrine cells, researchers were able to create beta cell-like cells that can secrete insulin. The reprogrammed cells were similar to beta cells in appearance, size, and shape; expressed genes characteristic of beta cells; and were able to partially restore blood sugar regulation in mice whose own beta cells had been chemically destroyed. While not transdifferentiation by definition, this method for reprogramming adult cells may be used as a model for directly reprogramming other adult cell types.

In addition to reprogramming cells to become a specific cell type, it is now possible to reprogram adult somatic cells to become like embryonic stem cells (induced pluripotent stem cells, iPSCs) through the introduction of embryonic genes. Thus, a source of cells can be generated that are specific to the donor, thereby increasing the chance of compatibility if such cells were to be used for tissue regeneration. However, like embryonic stem cells, determination of the methods by which iPSCs can be completely and reproducibly committed to appropriate cell lineages is still under investigation.

Many important questions about adult stem cells remain to be answered. They include:

Previous|IV. What are adult stem cells?|Next

View post:
What are adult stem cells? [Stem Cell Information]

Researchers have found a new source of stem cells that produce fat tissue, findings presented today at the European Congress of Endocrinology in Wrocaw, Poland, show. This unique in vitro human stem cell model of brown fat tissue could aid studies into how fat tissue develops and the development of new anti-obesity drugs.

There are two types of fat tissue found in humans: white adipose tissue (WAT) that accumulates lipids, and brown adipose tissue (BAT) that can burn lipids to produce heat. BAT is mainly found in babies, although recent studies show that adults may retain a small amount of BAT. BAT is considered important in obesity research as it represents a potential pathway by which the body can control metabolism by burning excess lipids to produce heat. Previously there have been no in vitro human models to aid research into BAT tissue development.

A team from the University of Florence in Italy studied patients with a rare tumor called pheochromocytoma. This tumor is found in the adrenal glands and causes the release of excess levels of the hormones adrenaline and noradrenaline. The team removed tumors from eight patients and examined the fat tissue that surrounded them. They found that, in addition to the WAT present in healthy people, pheochromocytoma patients also had some tissue with molecular markers for BAT cells present.

From this tissue, the team isolated and characterized brown adipose stem cells and compared their properties to precursor WAT cells from the same patient. Using gene expression analysis, immunophenotyping and differentiation tools, they found the two cell types had different properties, in particular in their potential to differentiate into BAT cells, thus indicating a different developmental pathway for the two types of fat cell.

This is an exciting discovery, said Professor Michaela Luconi, who led the research. Obesity is now a huge, worldwide health issue and we urgently need new treatment strategies to tackle it. Brown adipose tissue has long been seen as a potential target for new anti-obesity treatments as it is able to control metabolic rate and burn excess fat molecules.

Our research has characterized the first in vitro human model for brown adipose stem cells from a novel source. Our theory is that the excess adrenaline produced by this rare tumor may have induced the expansion of the brown adipose stem cell component present in this depot of white adipose tissue. We now need to carry out further work to see if this theory is correct and whether the process can be reproduced in the lab.

The team are currently unable to produce mature BAT cells from the brown adipose stem cells, but now plan to study how they can improve this differentiation process. This model has huge potential to allow us to learn more about how different types of fat cell develop, said Professor Luconi. Greater understanding of this process will aid us in designing and testing specific anti-obesity drugs targeting white to brown cells conversion.

Story Source:

The above post is reprinted from materials provided by European Society of Endocrinology. Note: Materials may be edited for content and length.

Visit link:
New source of fat tissue stem cells discovered -- ScienceDaily

Body fat contains regenerative stem cells that have the ability to revitalize and heal. A leader in the cosmetic enhancement field, the Center for Smart Lipo and Plastic Surgery in Langhorne, PA now offers fat transfer procedures that utilize stem cells. Patients achieve impressive results in body contouring and facial rejuvenation through the use of their own fat cells. Dr. Richard Goldfarb, an experienced and certified doctor at the facility, participates in ongoing research regarding the use of stem cells for cosmetic and non-cosmetic purposes.

About Stem Cells from Fat The web is filled with stories and articles about professional sports figures who have healed their injuries with fat-derived stem cells. Globally, many people are having fat taken from their bodies and using the stem cells within it to aid with different medical issues, such as wounds and muscular difficulties. The stem cells produced in fat are not the same as those found in embroyos, which is considered to be controversial. The adult body produces these cells in fat and also the bone marrow. They are very easy and inexpensive to harvest for medical purposes, without troubling ethical considerations.

Benefits of Fat Stem Cells Stem cells from fat can be used in several cosmetic procedures, such as augmentation of the buttocks and the breasts. It is also used to enhance the facial features, by smoothing out fine lines and wrinkles. The largest benefit to using fat is that it offers superior results over other methods. Using a persons own fat also increases its survival rate, which will help the results to last over the long term.

Anyone who is interested in receiving a fat stem cell cosmetic procedure should contact the experienced staff at the Center for Smart Lipo and Plastic Surgery for more information and a consultation.

Read the original post:
Fat Stem Cells - Center For SmartLipo & Plastic Surgery

An international team of researchers, with the participation of the University of Granada (UGR), has revealed new data on why breast cancer has a higher incidence and is more aggressive in obese people. The reason is that peritumoral fat (the fat around the tumor) facilitates the expansion and invasion of cancer stem cells (CSCs), which are responsible of the onset and growth of the tumor.

CSCs are found in tumors in a very small proportion, and their main characteristic is that they are responsible of metastasis originating in parts of the body far from the original tumor. Conventional chemotherapy and radiotherapy treatments are not capable of eliminating said CSCs, and for that, it's very common that, after the first response to the treatment, many cancer patients suffer a relapse.

This new research work has been lead by the University of Miami (Florida, United States), and it has counted with the participation of researchers from Granada's University Hospital Center and from the UGR "Terapias avanzadas: diferenciacin, regeneracin y cncer" (Advanced therapies: differentiation, regeneration and cancer) research team. Both groups of researchers belong to the Biosanitary Institute of Granada (ibs. GRANADA).

Mechanisms yet to be clarified

The consequences of the obesity epidemic on cancer morbidity and mortality are very serious. In fact, it is estimated that, nowadays, up to 20% of cancer-related deaths may be attributable to obesity.

Obese women have a greater risk of suffering breast cancer after menopause, and they have a worse progression of the disease no matter their age, but the mechanisms by which obesity contributes to the development and progression of cancer aren't clear yet. Obesity-related fat causes local inflammation and prevents adipocytes (the cells forming said fat) from maturing.

For this research, carried out in mice and published in the journal Cancer Research, researchers assessed the effects of coculturing adipocytes with breast cancer cells on tumor aggressivity, capacity of local invasion and metastatic potential of said tumor.

The results show that the interaction between tumor cells and immature adipocytes near the tumor during the first stages of breast cancer increased the secretion of cytokines (proinflammatory proteins).

"Said cytokines cause a greater expansion of highly metastatic CSCs," UGR professor Juan Antonio Marchal Corrales, one of the authors of this paper, explains.

Preclinical rationale

In addition, the researchers have described the mechanism by which this process takes place and its relation with the activation of the SRC Kinase protein. In turn, said protein induces the activation of the Sox2 transcription factor (essential to maintain stem cells characteristics) and of a small RNA molecule called miRNA-302b.

"The prolonged coculture of tumor cells with immature adipocytes or cytokines increased the proportion of CSCs (which had the ability to form new tumors), the presence of tumor cells in blood, and the metastatic potential after its implementation in mice -Marchal says-. And last, we found that SRC-Kinase-inhibiting drugs decrease the production of cytokines and CSCs."

These findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of SRC inhibitors for breast cancer treatment.

Story Source:

The above post is reprinted from materials provided by University of Granada. Note: Materials may be edited for content and length.

Read more here:
Breast cancer has a higher incidence in obese women ...

McMaster researchers have found one more reason to exercise: working out triggers influential stem cells to become bone instead of fat, improving overall health by boosting the body's capacity to make blood.

The body's mesenchymal stem cells are most likely to become fat or bone, depending on which path they follow.

Using treadmill-conditioned mice, a team led by the Department of Kinesiology's Gianni Parise has shown that aerobic exercise triggers those cells to become bone more often than fat.

The exercising mice ran less than an hour, three times a week, enough time to have a significant impact on their blood production, says Parise, an associate professor.

In sedentary mice, the same stem cells were more likely to become fat, impairing blood production in the marrow cavities of bones.

The research appears in a new paper published by the Journal of the Federation of American Societies for Experimental Biology.

"The interesting thing was that a modest exercise program was able to significantly increase blood cells in the marrow and in circulation," says Parise. "What we're suggesting is that exercise is a potent stimulus -- enough of a stimulus to actually trigger a switch in these mesenchymal stem cells."

The composition of cells in the bone marrow cavity has an important influence on the productivity of blood stem cells.

In ideal conditions, blood stem cells create healthy blood that boosts the immune system, permits the efficient uptake of oxygen, and improves the ability to clot wounds.

Bone cells improve the climate for blood stem cells to make blood.

But when fat cells start to fill the bone marrow cavity -- a common symptom of sedentary behavior -- blood stem cells become less productive, and conditions such as anemia can result.

The findings add to the growing list of established benefits of exercise, Parise says, and suggest that novel non-medicinal treatments for blood-related disorders may be in the future.

"Some of the impact of exercise is comparable to what we see with pharmaceutical intervention," he says. "Exercise has the ability to impact stem cell biology. It has the ability to influence how they differentiate."

Story Source:

The above post is reprinted from materials provided by McMaster University. Note: Materials may be edited for content and length.

Excerpt from:
Exercise boosts health by influencing stem cells to become ...

Adipose Stem Cell Therapy

What is an Autologous Adipose Stem Cell Procedure?

A small sample of Adipose tissue (fat) is removed from above the Superior Iliac spine (love handles) or abdomen under a local anesthetic.

Obtaining Adipose-Derived Stem Cells (ADSCs) is much easier and less invasive than performing abone marrowextraction. In addition, adipose tissue contains much larger volumes of mesenchymal stem cells than does bone marrow. We use the patient's own adipose tissue to extract the stem cells. Autologous meansthat the donor and the recipient are the same person.

Benefits of ADSCs: Stem cells play an integral part in wound healing and regeneration of tissue at the cellular level.

The Major Advantages of Adipose Stem Cell Therapy:

Is this procedure a significant improvement on other treatments currently available?

Yes We can now obtain Adult Stem Cells (ASCs) from a fat sample. This in-clinic treatment is completed the same day, and there is no need to ship samples to an outside laboratory and wait days for the cells to be returned for an injection on a second visit. This faster process provides increased stem cell counts, without manipulation.

Is an Autologous Adipose Stem Cell Procedure Safe?

Yes because the adipose tissue is removed from one's own body via sterile technique and remains in a controlled environment there are no problems with cell rejection or disease transmission. The interview, physical, harvesting, and administration of stem cells are all performed in-house under a physicians control.

How do I know if stem cell therapy is right for me?

Discussing treatment options with your physician is an important first step in making a decision regarding stem cell therapy. Potential outcomes, an integrative and comprehensive treatment plan, and financial costs are all factors to consider.

I have heard Stem Cell Treatments are VERY expensive, can I afford this?

Yes you can!

Due to our advanced adult stem cell technology provided in the form of an in house procedure, our Stem Cell Center can now provide this service at a fraction of the cost previously incurred. Even better, its a same day procedure.We offer theentirety of our treatment in Phoenix, Arizona -USA and we have been able to lower our cost to a flat rate of $7,100.00 per treatment (including consultation). Fees are subject to change and some more complex proceduresmay incur additional costs.

Why Choose an Adipose Stem Cell Procedure?

Adipose-derived mesenchymal stem cells areeasier to harvest than bone marrowand can be obtained in much larger quantities. In addition, it is much less painful and involves lower risks.

*There is a much shorter time from extraction to the administration oftreatment.No culturing or manipulation is needed using our procedure, as opposed to a bone marrow extraction which requires days or weeksto reach the necessary therapeutic threshold.

*There are no ethical or moral issues involved in harvesting autologous Adult Stem Cells (ASCs).

Are There Detrimental Side Effects from an Adipose Stem Cell Procedure?

No, the adipose tissue is extracted from the patients own body sono foreign donors are used. This minimizes the potential for immune rejection.Our procedure is performed completely in-house and administered by licensed physicians here in the United States. Please keep in mind that every procedure does have its risks, but we do practice sterile technique which makes the risk of infectionvery low.In fact, we have not had any infections develop in any of the stem cell patients we have treated as we take great care in keeping a sterile environment.

What You Can Expect When Visiting the Stem Cell Rejuvenation Center:

Differences Between An Adipose And A Bone Marrow Procedure:

Autologous Growth Factor Components of PRP:

Go here to see the original:
About Adipose Stem Cell Therapy

Stem cells extracted from body fat may pave the way for the development of new regenerative therapies including soft tissue reconstruction following tumor removal or breast mastectomy surgery, the development of tissue-engineered cartilage or bone, and the treatment of cardiovascular disease.

An interdisciplinary team of Queen's University researchers led by Dr. Lauren Flynn, a professor in the Departments of Chemical Engineering and Anatomy and Cell Biology, has been working with stem cells extracted from samples of human fat and is developing new methods in the lab to develop these cells into mature tissue substitutes.

While stem cells extracted from fat cannot be grown into as many different types of cells as embryonic stem cells, they do have a number of advantages.

"The advantages include less ethical controversy, abundant cell availability from discarded tissues from elective surgeries like breast reductions and tummy tucks, and a much reduced possibility for immune rejection when re-implanting cells extracted from a person's own fat," explains Dr. Juares Bianco, a postdoctoral fellow in the Department of Chemical Engineering and the Human Mobility Research Centre (HMRC) who is working in the Flynn lab group.

Sarah Fleming, a Master's candidate in the group, is also working to establish a new method for growing the fat stem cells in the lab using a system that mimics the natural tissue environment found within the body. This work is based on Dr. Flynn's development of a technique for washing away all traces of cells from a sample of body fat, leaving behind a three-dimensional tissue scaffold that she calls "decellularized adipose tissue," or "DAT" for short.

This empty scaffold can then be used for soft tissue reconstruction or as a growing environment for the extracted stem cells. Dr. Flynn's preliminary studies have shown that when the stem cells are grown on the DAT scaffold, they naturally begin to mature into fat cells, suggesting that the engineered growth environment influences the type of cell that the basic stem cells will turn into during the tissue regeneration process.

This research was funded in part by NSERC's Collaborative Research and Training Experience Program (CREATE) and was conducted by researchers in the Human Mobility Research Centre (HMRC). The HMRC is a partnership between Queen's University and Kingston General Hospital and serves as a point of collaboration between the disciplines of medicine, engineering, health sciences, and information technology.

Story Source:

The above post is reprinted from materials provided by Queen's University. Note: Materials may be edited for content and length.

See the rest here:
Extracting stem cells from fat for tissue regeneration ...

In a world first, Australian scientists have figured out how to reprogram adult bone or fat cells to form stem cells that could potentially regenerate any damaged tissue in the body.

The researchers were inspired by the way salamanders are able to replace lost limbs, and developed a technique that gives adult cells the ability to lose their adultcharacteristics, multiply and regenerate multiple cell types - what is known as multipotency.That means the new stem cells can hypothetically repairany injury in the body, from severed spinal cords to joint and muscle degeneration. And its a pretty big deal, because there are currently no adult stem cells that naturally regenerate multiple tissue types.

"This technique is a significant advance on many of the current unproven stem cell therapies, which have shown little or no objective evidence they contribute directly to new tissue formation," said lead researcher John Pimanda from the University of New South Wales, Faculty of Medicine (UNSW Medicine). "We are currently assessing whether adult human fat cells reprogrammed into [induced multipotent stem cells (iMS cells)] can safely repair damaged tissue in mice, with human trials expected to begin in late 2017."

Right now, although its an exciting and much-hyped field of study, stem cell therapy still has a number of limitations, primarily because the most useful cells are embryonic stem cells, which are taken from developing embryos and have the potential to become any cell type in the body.But they also have the tendency to form tumours and cannot be transplanted directly to regenerate adult cells.

Instead, researchers are able to use tissue-specific adult cells, which can only turn into the cell types in their region of the body for example, lung stem cells can only differentiate into lung tissue, so theyre not as versatile as scientists need.

Scientists have also worked out how to reprogram regular adult stem cells into induced pluripotent stem cells (iPS) a type of stem cell thats even more flexible than multipotent stem cells, but requires the use of viruses in order for the cells to be reset, which isnt ideal to help treat patients. Thats why the new research is so exciting.

"Embryonic stem cells cannot be used to treat damaged tissues because of their tumour forming capacity," said one of the researchers, Vashe Chandrakanthan. "The other problem when generating stem cells is the requirement to use viruses to transform cells into stem cells, which is clinically unacceptable."

"We believe weve overcome these issues with this new technique."

To create the new type of stem cells, the researchers collected adult human bone and fat cells and treated them with two compounds: 5-Azacytidine (AZA); and platelet-derived growth factor-AB (PDGF-AB) for two days.

This kick-started the process of dedifferentiation which basically means it started to revert them to a multipotent stem cell state. The cells were then kept in PDGF-AB for a few weeks while they slowly changed into stem cells, eventually becoming tissue-regenerative iMS cells which basically means they can repair any type of tissue in the body.

"This technique is ground-breaking because iMS cells regenerate multiple tissue types," said Pimanda. "We have taken bone and fat cells, switched off their memory and converted them into stem cells so they can repair different cell types once they are put back inside the body."

Right now, this process is only a proof of concept, but the researchers are already on their way to furthering the technique, and are currently investigating if human iMS cells can be transformed and repair tissue damage in mice.

The researchers also want to look into how the cells act at the sites of transplantation. If all goes well, human trials are expected for late 2017.

The first trials will focus on whether the iMS cells can heal bone, joint, and muscle tissue, helping to improve treatment for chronic back pain and injuries.

This research has been published in the Proceedings of the National Academy of Sciences.

UNSW Medicine is a sponsor of ScienceAlert. Find out more about their world-leading research.

Go here to read the rest:
New stem cell treatment using fat cells ... - ScienceAlert

Durham, NC A new study appearing in the current issue of STEM CELLS Translational Medicine indicates that stem cells harvested from fat (adipose) are more potent than those collected from bone marrow in helping to modulate the bodys immune system.

The finding could have significant implications in developing new stem-cell-based therapies, as adipose tissue-derived stem cells (AT-SCs) are far more plentiful in the body than those found in bone marrow and can be collected from waste material from liposuction procedures. Stem cells are considered potential therapies for a range of conditions, from enhancing skin graft survival to treating inflammatory bowel disease.

Researchers at the Leiden University Medical Centers Department of Immunohematology and Blood Transfusion in Leiden, The Netherlands, led by Helene Roelofs, Ph.D., conducted the study. They were seeking an alternative to bone marrow for stem cell therapies because of the low number of stem cells available in marrow and also because harvesting them involves an invasive procedure.

Adipose tissue is an interesting alternative since it contains approximately a 500-fold higher frequency of stem cells and tissue collection is simple, Dr. Roelofs said.

Moreover, Dr. Sara M. Melief added, 400,000 liposuctions a year are performed in the U.S. alone, where the aspirated adipose tissue is regarded as waste and could be collected without any additional burden or risk for the donor.

For the study, the team used stem cells collected from the bone marrow and fat tissue of age-matched donors. They compared the cells ability to regulate the immune system in vitro and found that the two performed similarly, although it took a smaller dose for the AT-SCs to achieve the same effect on the immune cells.

When it came to secreting cytokines the cell signaling molecules that regulate the immune system the AT-SCs also outperformed the bone marrow-derived cells.

This all adds up to make AT-SC a good alternative to bone marrow stem cells for developing new therapies, Dr. Roelofs concluded.

Cells from bone marrow and from fat were equivalent in terms of their potential to differentiate into multiple cell types, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of Wake Forest Institute for Regenerative Medicine. The fact that the cells from fat tissue seem to be more potent at suppressing the immune system suggest their promise in clinical therapies.

Read the original here:
Stem cells from fat outperform those from bone marrow in ...

Adult stem cellsee somatic stem cell.

Astrocytea type of supporting (glial) cell found in the nervous system.

BlastocoelThe fluid-filled cavity inside the blastocyst, an early, preimplantation stage of the developing embryo.

BlastocystA preimplantation embryo of about 150 cells produced by cell division following fertilization. The blastocyst is a sphere made up of an outer layer of cells (the trophoblast), a fluid-filled cavity (the blastocoel), and a cluster of cells on the interior (the inner cell mass).

Bone marrow stromal cellsA population of cells found in bone marrow that are different from blood cells, a subset of which are multipotent stem cells, able to give rise to bone, cartilage, marrow fat cells, and able to support formation of blood cells.

Bone marrow stromal cellsA population of cells found in bone marrow that are different from blood cells, a subset of which are multipotent stem cells, able to give rise to bone, cartilage, marrow fat cells, and able to support formation of blood cells.

Bone marrow stromal stem cells (skeletal stem cells)A multipotent subset of bone marrow stromal cells able to form bone, cartilage, stromal cells that support blood formation, fat, and fibrous tissue.

Cell-based therapiesTreatment in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cells or tissues.

Cell cultureGrowth of cells in vitro in an artificial medium for research or medical treatment.

Cell divisionMethod by which a single cell divides to create two cells. There are two main types of cell division depending on what happens to the chromosomes: mitosis and meiosis.

Chromosomea structure consisting of DNA and regulatory proteins found in the nucleus of the cell. The DNA in the nucleus is usually divided up among several chromosomes.The number of chromosomes in the nucleus varies depending on the species of the organism. Humans have 46 chromosomes.

Clone (v) To generate identical copies of a region of a DNA molecule or to generate genetically identical copies of a cell, or organism; (n) The identical molecule, cell, or organism that results from the cloning process.

CloningSee Clone.

Cord blood stem cellsSee Umbilical cord blood stem cells.

Culture mediumThe liquid that covers cells in a culture dish and contains nutrients to nourish and support the cells. Culture medium may also include growth factors added to produce desired changes in the cells.

DifferentiationThe process whereby an unspecialized embryonic cell acquires the features of a specialized cell such as a heart, liver, or muscle cell. Differentiation is controlled by the interaction of a cell's genes with the physical and chemical conditions outside the cell, usually through signaling pathways involving proteins embedded in the cell surface.

Directed differentiationThe manipulation of stem cell culture conditions to induce differentiation into a particular cell type.

DNADeoxyribonucleic acid, a chemical found primarily in the nucleus of cells. DNA carries the instructions or blueprint for making all the structures and materials the body needs to function. DNA consists of both genes and non-gene DNA in between the genes.

EctodermThe outermost germ layer of cells derived from the inner cell mass of the blastocyst; gives rise to the nervous system, sensory organs, skin, and related structures.

EmbryoIn humans, the developing organism from the time of fertilization until the end of the eighth week of gestation, when it is called a fetus.

Embryoid bodiesRounded collections of cells that arise when embryonic stem cells are cultured in suspension. Embryoid bodies contain cell types derived from all 3 germ layers.

Embryonic germ cellsPluripotent stem cells that are derived from early germ cells (those that would become sperm and eggs). Embryonic germ cells (EG cells) are thought to have properties similar to embryonic stem cells.

Embryonic stem cellsPrimitive (undifferentiated) cells derived from a 5-day preimplantation embryo that are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.

Embryonic stem cell lineEmbryonic stem cells, which have been cultured under in vitro conditions that allow proliferation without differentiation for months to years.

EndodermThe innermost layer of the cells derived from the inner cell mass of the blastocyst; it gives rise to lungs, other respiratory structures, and digestive organs, or generally "the gut."

Enucleatedhaving had its nucleus removed.

Epigenetichaving to do with the process by which regulatory proteins can turn genes on or off in a way that can be passed on during cell division.

Feeder layerCells used in co-culture to maintain pluripotent stem cells. For human embryonic stem cell culture, typical feeder layers include mouse embryonic fibroblasts (MEFs) or human embryonic fibroblasts that have been treated to prevent them from dividing.

FertilizationThe joining of the male gamete (sperm) and the female gamete (egg).

FetusIn humans, the developing human from approximately eight weeks after conception until the time of its birth.

GameteAn egg (in the female) or sperm (in the male) cell. See also Somatic cell.

Gastrulationthe process in which cells proliferate and migrate within the embryo to transform the inner cell mass of the blastocyst stage into an embryo containing all three primary germ layers.

GeneA functional unit of heredity that is a segment of DNA found on chromosomes in the nucleus of a cell. Genes direct the formation of an enzyme or other protein.

Germ layersAfter the blastocyst stage of embryonic development, the inner cell mass of the blastocyst goes through gastrulation, a period when the inner cell mass becomes organized into three distinct cell layers, called germ layers. The three layers are the ectoderm, the mesoderm, and the endoderm.

Hematopoietic stem cellA stem cell that gives rise to all red and white blood cells and platelets.

Human embryonic stem cell (hESC)A type of pluripotent stem cell derived from the inner cell mass (ICM) of the blastocyst.

Induced pluripotent stem cellsSomatic (adult) cells reprogrammed to enter an embryonic stem celllike state by being forced to express factors important for maintaining the "stemness" of embryonic stem cells (ESCs). Mouse iPSCs were first reported in 2006 (Takahashi and Yamanaka), and human iPSCs were first reported in late 2007 (Takahashi et al. and Yu et al.). Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including the expression of stem cell markers, the formation of tumors containing cells from all three germ layers, and the ability to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers. Scientists are actively comparing iPSCs and ESCs to identify important similarities and differences.

In vitroLatin for "in glass"; in a laboratory dish or test tube; an artificial environment.

In vitro fertilizationA technique that unites the egg and sperm in a laboratory instead of inside the female body.

Inner cell mass (ICM)The cluster of cells inside the blastocyst. These cells give rise to the embryo and ultimately the fetus. The ICM cells are used to generate embryonic stem cells.

Long-term self-renewalThe ability of stem cells to replicate themselves by dividing into the same non-specialized cell type over long periods (many months to years) depending on the specific type of stem cell.

Mesenchymal stem cellsCells from the immature embryonic connective tissue. A number of cell types come from mesenchymal stem cells, including chondrocytes, which produce cartilage.

MeiosisThe type of cell division a diploid germ cell undergoes to produce gametes (sperm or eggs) that will carry half the normal chromosome number. This is to ensure that when fertilization occurs, the fertilized egg will carry the normal number of chromosomes rather than causing aneuploidy (an abnormal number of chromosomes).

MesodermMiddle layer of a group of cells derived from the inner cell mass of the blastocyst; it gives rise to bone, muscle, connective tissue, kidneys, and related structures.

MicroenvironmentThe molecules and compounds such as nutrients and growth factors in the fluid surrounding a cell in an organism or in the laboratory, which play an important role in determining the characteristics of the cell.

MitosisThe type of cell division that allows a population of cells to increase its numbers or to maintain its numbers. The number of chromosomes remains the same in this type of cell division.

MultipotentHaving the ability to develop into more than one cell type of the body. See also pluripotent and totipotent.

Neural stem cellA stem cell found in adult neural tissue that can give rise to neurons and glial (supporting) cells. Examples of glial cells include astrocytes and oligodendrocytes.

NeuronsNerve cells, the principal functional units of the nervous system. A neuron consists of a cell body and its processesan axon and one or more dendrites. Neurons transmit information to other neurons or cells by releasing neurotransmitters at synapses.

OligodendrocyteA supporting cell that provides insulation to nerve cells by forming a myelin sheath (a fatty layer) around axons.

ParthenogenesisThe artificial activation of an egg in the absence of a sperm; the egg begins to divide as if it has been fertilized.

PassageIn cell culture, the process in which cells are disassociated, washed, and seeded into new culture vessels after a round of cell growth and proliferation. The number of passages a line of cultured cells has gone through is an indication of its age and expected stability.

PluripotentHaving the ability to give rise to all of the various cell types of the body. Pluripotent cells cannot make extra-embryonic tissues such as the amnion, chorion, and other components of the placenta. Scientists demonstrate pluripotency by providing evidence of stable developmental potential, even after prolonged culture, to form derivatives of all three embryonic germ layers from the progeny of a single cell and to generate a teratoma after injection into an immunosuppressed mouse.

Polar BodyA polar body is a structure produced when an early egg cell, or oogonium, undergoes meiosis. In the first meiosis, the oogonium divides its chromosomes evenly between the two cells but divides its cytoplasm unequally. One cell retains most of the cytoplasm, while the other gets almost none, leaving it very small. This smaller cell is called the first polar body. The first polar body usually degenerates. The ovum, or larger cell, then divides again, producing a second polar body with half the amount of chromosomes but almost no cytoplasm. The second polar body splits off and remains adjacent to the large cell, or oocyte, until it (the second polar body) degenerates. Only one large functional oocyte, or egg, is produced at the end of meiosis.

PreimplantationWith regard to an embryo, preimplantation means that the embryo has not yet implanted in the wall of the uterus. Human embryonic stem cells are derived from preimplantation-stage embryos fertilized outside a woman's body (in vitro).

ProliferationExpansion of the number of cells by the continuous division of single cells into two identical daughter cells.

Regenerative medicineA field of medicine devoted to treatments in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cell populations or tissues. (See also cell-based therapies).

Reproductive cloningThe process of using somatic cell nuclear transfer (SCNT) to produce a normal, full grown organism (e.g., animal) genetically identical to the organism (animal) that donated the somatic cell nucleus. In mammals, this would require implanting the resulting embryo in a uterus where it would undergo normal development to become a live independent being. The first animal to be created by reproductive cloning was Dolly the sheep, born at the Roslin Institute in Scotland in 1996. See also Somatic cell nuclear transfer (SCNT).

SignalsInternal and external factors that control changes in cell structure and function. They can be chemical or physical in nature.

Somatic cellany body cell other than gametes (egg or sperm); sometimes referred to as "adult" cells. See also Gamete.

Somatic cell nuclear transfer (SCNT)A technique that combines an enucleated egg and the nucleus of a somatic cell to make an embryo. SCNT can be used for therapeutic or reproductive purposes, but the initial stage that combines an enucleated egg and a somatic cell nucleus is the same. See also therapeutic cloning and reproductive cloning.

Somatic (adult) stem cellsA relatively rare undifferentiated cell found in many organs and differentiated tissues with a limited capacity for both self renewal (in the laboratory) and differentiation. Such cells vary in their differentiation capacity, but it is usually limited to cell types in the organ of origin. This is an active area of investigation.

Stem cellsCells with the ability to divide for indefinite periods in culture and to give rise to specialized cells.

Stromal cellsNon-blood cells derived from blood organs, such as bone marrow or fetal liver, which are capable of supporting growth of blood cells in vitro. Stromal cells that make the matrix within the bone marrow are also derived from mesenchymal stem cells.

SubculturingTransferring cultured cells, with or without dilution, from one culture vessel to another.

Surface markersProteins on the outside surface of a cell that are unique to certain cell types and that can be visualized using antibodies or other detection methods.

Teratoma A multi-layered benign tumor that grows from pluripotent cells injected into mice with a dysfunctional immune system. Scientists test whether they have established a human embryonic stem cell (hESC) line by injecting putative stem cells into such mice and verifying that the resulting teratomas contain cells derived from all three embryonic germ layers.

Therapeutic cloningThe process of using somatic cell nuclear transfer (SCNT) to produce cells that exactly match a patient. By combining a patient's somatic cell nucleus and an enucleated egg, a scientist may harvest embryonic stem cells from the resulting embryo that can be used to generate tissues that match a patient's body. This means the tissues created are unlikely to be rejected by the patient's immune system. See also Somatic cell nuclear transfer (SCNT).

TotipotentHaving the ability to give rise to all the cell types of the body plus all of the cell types that make up the extraembryonic tissues such as the placenta. (See also Pluripotent and Multipotent).

TransdifferentiationThe process by which stem cells from one tissue differentiate into cells of another tissue.

TrophectodermThe outer layer of the preimplantation embryo in mice. It contains trophoblast cells.

TrophoblastThe outer cell layer of the blastocyst. It is responsible for implantation and develops into the extraembryonic tissues, including the placenta, and controls the exchange of oxygen and metabolites between mother and embryo.

Umbilical cord blood stem cellsstem cells collected from the umbilical cord at birth that can produce all of the blood cells in the body (hematopoietic). Cord blood is currently used to treat patients who have undergone chemotherapy to destroy their bone marrow due to cancer or other blood-related disorders.

UndifferentiatedA cell that has not yet developed into a specialized cell type.

Visit link:
Glossary [Stem Cell Information]