Because type 1 diabetes is the result of inability of pancreatic islet cells to produce insulin, one obvious solution would be to transplant a functional pancreas into the diabetic patient. Yet, due to the multiple risks of organ availability, organ transplantation, immune-rejection, and the need for lifelong drug-induced immunosuppression, this is not generally a viable option. One alternative, which reduces the risk of complications from the highly-invasive organ transplantation, has been the transplantation of islet cells into the portal vein of the liver. This method has seen success, yet still faces a number of problems, including the fact that a long-term regimen of immunosuppressive drugs is still necessary to prevent an immune reaction to the foreign tissue. Furthermore, there are simply not enough islet cells available as it requires at least two cadaveric donors for each transplant.
Researchers at the CDRP are currently trying to solve these problems through a number of avenues:
Islet cell encapsulation
To address the problem of immuno-rejection following the transplantation of foreign islet cells, a team of CDRP researchers, including Dr. Emmanuel Opara, Dr. Georgia Papavasiliou, Dr. Eric Brey, and Dr. Victor Perez-Luna are developing methods and materials for the encapsulation of islet cells. The biocompatible capsules under development will have the dual ability to release insulin through pores while providing protection from immune recognition and activation.
The group is simultaneously working on methods to scale-up the process of encapsulation and biosensors to determine the functional level of the encapsulated islets.
Vascularization of transplanted islet cells
Once new islet cells are transplanted, the next major hurdle is the prevention of cellular death. Because there is no existing vasculature to support these exogenous islet cells, they will not have an adequate supply of nutrients and oxygen unless they are heavily vasularized. Dr. Eric Brey and his research team, in collaboration with Dr. Emmanuel Opara, are working on ways to promote vascularization and keep these islet cells alive.
Islet cell availability
To address the problem of islet cell availability, Dr. Emmanuel Opara recently developed a method for efficiently isolating porcine islet cells. Barriers to using porcine cells, which produce a form of insulin very similar to that of humans, have included the unique difficulties surrounding their isolation and purification. Dr. Opara has now significantly reduced this particular barrier.
Stem cell differentiation
Another source of human islet cells is the derivation of these cells from human stem cells. Dr. Rong Wang is currently working toward this goal—along with collaborators at IIT, she is investigating the optimal surface properties and molecular supplementation to encourage differentiation into beta cells. If Wang can successfully direct the differentiation of commercially-available stem cells into beta cells for transplantation, a next step might be to use adult stem cells with pluripotency. If successful, it is possible that eventually a patient’s own cells could be used. This would eliminate the risk of immuno-rejection, one of the biggest hurdles to a bioartificial pancreas.