Islet Transplantation & Cell Biology
Translational Research to Cure Diabetes
Type 1 diabetes develops after insulin-producing beta cells in the pancreas are destroyed. One of the most promising areas of diabetes research involves beta-cell replacement to restore insulin production.
Research in the Section on Islet Transplantation and Cell Biology is truly “bench to bedside,” as investigators apply insights gained through basic research to clinical studies aimed at improving the success of islet-cell transplantation and beta-cell regeneration.
Bolstering Beta Cells
A major challenge in islet-cell transplantation is a dearth of donor pancreases, which are necessary for harvesting islet cells. Researchers in the section are conducting studies to identify other sources of insulin-producing cells.
One team has already succeeded in producing new islet cells from precursor pancreatic duct cells harvested from human donor tissue. Efforts now are focused on expanding the supply of these cells so that a sufficient quantity is available for transplantation. Another team is determining whether mouse embryonic stem cells can be coaxed into becoming functional beta cells.
Although approaches vary, these studies should be aided by the recent discovery in the section of a molecule known as mMafA, which is a key transcription factor for beta cells. Research indicates that mMafA not only is one of the major signals that activates the insulin gene, but also appears to play an important role in islet-cell development.
The function of the insulin-producing cells is highly specialized but can become impaired easily. Investigators are conducting studies to understand what function-impairing changes actually occur with hyperglycemia, and in the course of islet-cell isolation, encapsulation and transplantation, and how to prevent or reverse these changes
In addition, investigators are evaluating strategies that might make it possible one day to work with a patient’s own cells and tissues to restore beta-cell functioning. Researchers use an animal model of pancreas regeneration to understand how to stimulate new growth of the islets. Recent studies done elsewhere indicate that it may be possible to convert liver cells into insulin-producing cells; researchers in the section are now studying this approach. In related work, another group in the section is studying whether cells from the pituitary gland can be re-engineered to behave like insulin-producing beta cells.
Protecting and Isolating Islet CellsResearchers in the section collaborate with colleagues in Joslin’s Section on Immunology and Immunogenetics and other Harvard investigators to develop strategies to protect transplanted islet cells from autoimmune attack and rejection. This work ranges from basic research into immune-system cells to clinical studies to improve transplantation success rates in people.
One team in the section is conducting animal studies to assess the effectiveness of various methods to encapsulate islet cells before transplantation to provide a barrier against immune system attack. Another Joslin researcher has identified a class 1 antigen that appears to increase the susceptibility of insulin-producing beta cells to autoimmune attack and destruction. This laboratory work might one day provide a target for drug development.
Scientists in the section have been collaborating with colleagues at the Clinical Islet Transplantation Program at Harvard Medical School to increase the success of islet transplantation in people. The Human Islet Facility at Joslin uses donated pancreases to isolate islet cells, which have been successfully transplanted into a small number of patients with type 1 diabetes.