StemCell Therapy

Encapsulated human embryonic stem-cell differentiated beta cell clusters (hES-C) show promise for treating diabetics without having to chronically suppress their immune system. A team of researchers at the University of California at San Francisco has now made the first nanoporous polymer thin-film encapsulation device containing human stem-cell derived -like cells that does not activate or sensitize immune cells, but which allows oxygen, nutrients, glucose and insulin to be exchanged. The device appears to work for up to six months after being transplanted in mice.

Diabetes mellitus is an auto-immune disease that leads to -cells being destroyed in type-1 diabetes and progressive -cell dysfunction in type-2 diabetes. The result is insulin insufficiency in the patient. Current treatments rely on closely monitoring blood glucose levels and then injecting insulin to simulate natural insulin secretion by pancreatic -cells. This approach is far from ideal, however, and often fails to keep glucose levels within the tight physiological range required. Complications such as potentially fatal hypoglycaemia can ensue, as well as various pathologies (such as cardiovascular disease, kidney failure, retinopathy and neuropathy) linked to repeated hyperglycaemic episodes.

Although pancreas and pancreatic islet transplants are an effective alternative to T1D patients, it is difficult to find donors. What is more, the patients own immune system needs to be chronically suppressed so that it does not reject the transplant.

Human embryonic stem cells (hES) or induced pluripotent stem cells (iPSC)-derived insulin-producing cells could be an alternative to whole organ and islet transplants, but again there are challenges to overcome. For one, researchers need to find a way to deal with teratoma formation and immune rejection. Cell encapsulation is showing promise here since it provides a physical barrier between transplanted hES-derived cell clusters (hES-C) and the patient, something that provides protection from his or her immune response.

The ideal cell encapsulation device should allow sufficient oxygen and nutrients to pass through it while allowing glucose and insulin to be transported so that blood glucose can be properly controlled. At the same time, however, it needs to stop immune cells, antibodies and pro-inflammatory cytokines from entering it. And of course, it needs to be biocompatible.

Researchers led by Tejal Desai have now made such a device. They began by growing zinc oxide nanorods on a silicon wafer that they then coated with a thin polymer solution. Next, they etched away the zinc oxide rods and lifted the nanoporous film that had been produced off the surface of the wafer. They then heat-sealed two of these nanoporous thin films in a bilaminar configuration and customized the size and shape of the device to fit the site in which it was to be transplanted.

The thin films are just 10 microns thick, making this the thinnest cell macro-encapsulation device to date, says lead author of the study Ryan Chang. By minimizing the thickness, we reduce the distance that nutrients, insulin and glucose have to cross. What is more, the polymer material itself, which has micro-architectures on its surface, promotes vascularization and provokes only a minimal foreign body response as observed in an in vivo study that we carried out lasting four months.

Of course, as with any stem cell therapy, safety comes first, he tells nanotechweb.org. We showed that the device effectively confines undifferentiated stem cells within it and prevents teratomas from escaping and spreading.

It could make for an essential core technology in allowing diabetics to become completely insulin independent, he adds.

The team, reporting its work in ACS Nano DOI: 10.1021/acsnano.7b01239, says that it is now busy scaling up the device in larger animal models and engineering transplant sites for further testing.

See the rest here:
Nanoporous thin-film device could help treat diabetes - nanotechweb.org

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