There is much that is unknown about β-cell biology in the context of regeneration, but through the use of powerful tools such as flow cytometry and adenoviral gene infection of human pancreatic islets, Drs. George and Boerner are tapping into a very influential field of medicine.
They hope that their studies will enable the identification of new methods to proliferate human islets. This is no easy task. It is well known within the field of pancreas research that β-cells are one of the most difficult cells types to maintain in vitro. β-cells are very sensitive to their environment and once removed from their home within the pancreas, they quickly begin to lose their function and eventually de-differentiate into other cell types.
An additional goal of this project will be to determine what factors will help stabilize β-cell function and physiology in vitro so that they are able to replicate in order to generate more tissue for further research and ideally to provide more tissue to enhance the outcomes of islet transplantation.
Two types of islet transplants are currently practiced, allogeneic and autologous islet transplants, both of which have vast therapeutic and scientific potential. Allogeneic islet transplantation, removal of pancreatic islets from the pancreas of a deceased organ donor and then transplanted into a recipient, is currently offered as an experimental treatment procedure to those suffering from pancreatitis or type 1 diabetes. This procedure is of much interest to clinicians as it offers the potential to allow patients with type 1 diabetes to become insulin indepenant that, in turn, improves their long-term outcomes. With low success rates and high numbers of side effects and complications, this procedure needs a substantial amount of fine-tuning before it can be offered as a reliable treatment source for type I diabetes.
Autologous islet transplants utilize the patient’s own tissue for transplantation. When the pancreas is removed from a patient, the tissue is immediately taken back to the clinical laboratory where islet cells are isolated, purified, and then transplanted back into the patient. As an accepted form of therapy for those suffering from chronic pancreatitis, this procedure offers benefits that allogenic procedures cannot, such as avoidance of systemic immune suppression, decreased chance of rejection, and slightly higher success rates. Although these are exciting ventures in the transplant realm, both procedures require a substantial amount of research to enrich their potential as therapies for type 1 diabetes.
Drs. Boerner and George are working to identify new methods that will enable researchers to multiply human islets while still maintaining their differentiated β-cell state in vitro. An important finding has shown that the long-term outcome of islet transplants directly correlates to number of islets that are transplanted. Thus, the more healthy islets that are transplanted, the better the patients’ outcome. They hope that their research will lead to vital outcomes that will allow for more successful islet transplants. These same methods can also be used to generate viable human islets for research purposes.
Dr. Brian Boerner's Work - Can β-cells be grown outside of the body? If so, what is the best environment to help them grow and function?
Dr. Nick George's Work - How do molecular pathways, such as the Hippo Pathway, affect β-cell development, maintenance, and regeneration?
- Focus Areas