StemCell Therapy

This past month, while on the lecture circuit, I again heard many wild claims about how many more stem cells there were in fat thanbone marrow. The most recent claims now have this fat stem cell count number at 2,000 times more stem cells in fat. Are any of these numbers correct? Where did all of this information come from?

First, as youve read here, bone marrow stem cells are better for creating cartilage than fat stem cells with 13 papers published as of this week that back that statement up. We also have far more research that bone marrow works well to help orthopedic injuries than we have for fat stem cells. In addition, when weve used fat stem cells in the past weve been unimpressed.So lets explore the differences in stem cell content between the two in more depth.

When I asked a very knowledgeable physician who had a slide in his presentation that stated that fat had 2,000 X more stem cells where this slide came from, it turned out that it was prepared by the manufacturer of a fat stem cell processing device. When we both tried to search to find a reference to back this up, there was no scientific evidencethat supported this claim. However, since digging further into this issue, I think Ive found where the confusion began and how its been exploited by fat stem cell advocates without serious challenge.So where does this information come from? To begin that journey you first have to learn a bit about how many stem cells there are in fat.

As Ive blogged before, stem cell counts in fat are often wildly inflated. This seems to happen when less sophisticated flow cytometry devices run by scientists who should know better erroneously count a fat or oil droplet as a stem cell. Confusion is also abundant in how best to count stem cells in the first place. For example, do you count them using a simple culture technique called CFU analysis or with a more sophisticated machine called a flow cytometer? Each has its strengths and weaknesses. One of the problems with comparing fat and bone marrow stem cell counts is that since the stem cells from each source grow at different rates, using a culture based method where you grow cells (the CFU method) is fraught with apples to oranges error issues. Hence, for this discussion well use flow cytometry to discover the real differences between fat and bone marrow stem cell content. This is a complex machine that counts the markers on the stem cells, one by one, but very quickly.

First, lets just look at mesenchymal stem cell (MSC) content. MSCs represent about 1-5% of the total nucleated cells in fat versus 0.1-0.5% for bone marrow. This has not only been published, but its also consistent with what we see in our lab when we look at the MSC content of both tissues. So thats 10X more MSCs in fat than bone marrow. However, we have to be careful with that number, as there are many more nucleated cells in bone marrow. How many more? In one study each ml of bone marrow had about 1,000 times more nucleated cells per mg (roughly a ml) of fat. In fact, its this huge disparity in the total number of cells in each tissue that causes the nutty comparison numbers discussed above. For example, if you try to look at the percentageof stem cellsout of bone marrow that form colonies in culture (the CFU number), its going to be minuscule compared to fat. However, this is expressed as a percentage of total cells, which are 1,000 times greater in bone marrow! Even the flow cytometry data above is expressed as a percentage of the total cells being counted, with there being many more cells per ml in bone marrow. So the numeric advantage of a higher percentage of MSCs relative to the total cells in fat is washed away by the fact that there are far fewer total cells in fat. Now lets look atthe other stem cells found in bone marrow that arent present in fat.

Bone marrow contains not only MSCs, but also Hematopoietic Stem Cells (HSCs) which Ive blogged on previously are quite good at muscle repair. These arent found in fat in any significant quantity. How many of these HSCs are there in bone marrow? They represent about 1%+ of the total nucleated cells. So for our proprietary method of isolating stem cells from bone marrow, on averagewe get around 150 million total cells per ml of isolate injected (thats only from one of the fractions in bone marrow that we isolate). So thats 1.5 million HSCs per ml injected. Bone marrow also has endothelial progenitor cells (EPCs), which are key in creating new blood supply, which is often critical for chronic orthopedic injuries, many of which dont heal because they happen in areas of poor blood supply. Finally, bone marrow also contains the newly discovered OCR cell which is specific for orthopedic tissue repair.

So does fat really have 2,000 times more stem cells than bone marrow? Nope. Does it have 500 times or even 10 times more? Nope. In fact, if you adjust for the fact that there are 1,000 more cells per unit volume in bone marrow than fat, the concept that fat has any more MSCs than bone marrow seems like a weak argument. In addition, once youadd in the fact that bone marrow has three stem cell types critical for orthopedic tissue repair that arent present in abundance in fat, the fat has more stem cells argument gets even weaker. The HPCs in bone marrow alone (without the EPCs and OCR cells) shows that bone marrow has more orthopedic injury relevant stem cells than fat. If you then look at studies showing that bone marrow MSCs outperform fat MSCs for things like cartilage repair, the case for using fat stem cells to treat orthopedic injuries becomes extremelyweak.

The upshot? The idea that fat has dramatically more stem cells than bone marrow seems like a lot of things these days in the stem cell wild west an urban myth. The mythseems to have been perpetuated by adipose stem cell advocates who began to compare the percentage of MSCs in fat to bone marrow using the proportion of MSCs to total cells found in the tissue. The proponents of the fat has more stem cells myth then left out a critical number that bone marrow has 1,000 times more cells per unit volume than fat. Oops! They also left out the fact that there are other relevant stem cells in bone marrow that arent in fat. In the end, when you look at the comparison critically, there are just as many if not more stem cells in bone marrow than fat!

Originally posted here:
The Fat Stem Cell Count Mirage... - Regenexx

This entry was posted on June 15, 2015 at 8:46 am and is filed under Fat Stem Cells. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |