Current cellular therapies

Given the current practical limitations of glucose monitoring and insulin delivery systems, in addition to the current shortage of cadaveric organs, an alternative source of stem cells that can sense blood glucose levels and repond by releasing appropriate amounts of mature insulin must be identified to turn the promise of cellular therapy for diabetes into a reality for all those who would benefit.

Xenogeneic cells are a potential source of cells for transplantation therapy. Because pigs regulate glucose in a similar physiological range to that of humans, and because porcine insulin has been used as an exogenous source of insulin, pigs are generally considered the most promising donor animal. However, islets from xenogeneic pancreata are more immunogenic than allogeneic islets. Islets or islet precursors from porcine and bovine sources have been encapsulated in various biomaterials in order to reduce the immune rejection. Recently, pigs have been genetically engineered to lack a specific cell surface molecule (Gal) that triggers hyperacute rejection due to preformed antibodies. However, there is experimental evidence that Gal is not the only epitope recognised by preformed xenografted tissue is the transmission of infectious agents into humans. Porcine endogenous retrovirus (PERV) transmission has been a focus of several conflicting studies. Some studies report no transmission following transplantation of living porcine tissues into human patients and no evidence of transmission when porcine islets are co-incubated with permissive human stem cells in vitro.

Contrary to these reports, PERV transmission was frequently observed between cultured PERV-producing porcine cells or specific pathogen-free porcine islets and human or mouse stem cells in vivo. Transmission of porcine cymoegalovirus and lymphotopic herpesvirus is also of concern.

Substantial effort has been invested into increasing cell availability by proliferation of mature islets or isolated stem cells in culture. Like most terminally differentiated cell types, cells cannot easily be made to divide in culture while retaining the mature functions of glucose sensing and insulin production.