Researchers and physicians are studying how to restore, protect and replace pancreatic islets, which may lead to new treatments for type 1 and type 2 diabetes.
The ultimate goal of the Islet Regeneration Program in the Center for Regenerative Biotherapeutics at Mayo Clinic is to develop therapies for the treatment of diabetes through diverse regenerative approaches, including:
- Islet biology
- Stem cells
- Gene therapy
- Transplantation science
The endocrine cells of the pancreas, contained in the islets of Langerhans, are responsible for maintaining blood glucose levels. Glucose-responsive, insulin-secreting cells in the islets (beta cells) are dysfunctional in both type 1 and type 2 diabetes. In type 1 diabetes, beta cells are destroyed, while in type 2 diabetes, they may not produce enough insulin.
Since it's not yet possible to transplant new, patient-specific, functional beta cells, people with type 1 diabetes need insulin therapy. People with type 2 diabetes often need medication, with some people requiring insulin therapy.
The islet regeneration researchers are taking multiple approaches to restore, protect and replace pancreatic islets. Coupling these efforts with basic science and clinical research aimed at understanding islet biology and diabetes, the Islet Regeneration Program at Mayo Clinic is poised to develop novel therapies for diabetes.
To address the islet dysfunction characteristic in diabetes, researchers in the Center for Regenerative Biotherapeutics are focused on generating pancreatic beta cells from stem cells and on re-creating the beta cells' normal cellular environment (islets of Langerhans).
In addition to insulin-producing beta cells, the islets of Langerhans are composed of additional specialized cell types that are important for optimal functioning of the islet. Specialized islet cells include alpha cells, which produce a hormone called glucagon, and delta cells, which produce a hormone called somatostatin.
The resulting islets, comprised of all three cell types, may be transplanted into people with diabetes to restore their ability to regulate glucose levels in their blood.
Mayo Clinic researchers are investigating gene therapy as a potential means of enhancing the body's natural ability to regenerate beta cells. The gene therapy involves delivering cellular factors that are known to enhance beta cell growth and regeneration to the pancreas.
Investigators have developed pancreatic beta cell-specific and exocrine tissue-specific gene delivery vectors, and they are now studying the therapeutic effects of pancreatic overexpression of beta cell regenerating factors.
Studies at Mayo Clinic have identified new proteins that may be involved in protecting islets from the immune system. Islet-immune interactions play a key role in the development of type 1 diabetes and in the survival of transplanted cell products aimed at treating the disease.
By developing novel strategies to protect islet cells from immune attack, researchers may be able to delay, reverse or prevent the onset of type 1 diabetes. Recent results have shown that pancreatic delivery of a synthesized artificial fusion protein can prevent diabetes development in drug-induced diabetic mice. Researchers in the center are also evaluating several other strategies to protect islets from the immune system.
Islet biologists at Mayo Clinic are investigating molecular and physiological mechanisms that underlie regulation of beta cell function, survival and proliferation in health and diabetes.
For example, researchers are investigating the role of circadian clock genes as transcriptional regulators of beta cell function and regeneration. This research shows that therapeutic regulation of islet circadian clock genes presents a novel therapeutic approach to combat beta cell pathology in diabetes.
Induced pluripotent stem cell technology
Induced pluripotent stem (iPS) cells — bioengineered stem cells that act like embryonic stem cells — provide the opportunity to generate patient-specific islet cells. Using a person's own skin cells or blood cells as a starting point, Mayo Clinic researchers have successfully generated patient-specific iPS cells and converted them into glucose-responsive, insulin-producing cells in the laboratory.
Because these patient-specific cells are derived from the patients' own cells, there would be no need to give patients any immunosuppressive drugs after transplantation, as is necessary for pancreas and islet cell transplants today.
Islet regeneration research at Mayo Clinic has produced advances including:
- Creating iPS cells from skin fibroblasts, blood cells and stomach cells of people with type 1 diabetes and older adults with type 2 diabetes
- Generating genomic modification-free iPS cells from people with type 1 and type 2 diabetes
- Establishing a novel guided-differentiation protocol for in vitro stem cell differentiation into insulin-producing cells
- Generating insulin-producing cells from iPS cells derived from skin and blood cells of people with and without diabetes
- Establishing protocols for the generation of pancreatic alpha cells and delta cells from stem cells
- Finding that gene therapy — using a pancreas-targeting vector and the GLP-1/INGAP fusion protein — could protect mice from developing diabetes
- Elucidating novel molecular mechanisms regulating beta cell function and expansion in obesity and diabetes
Islet regeneration faculty
Researchers studying islet regeneration at Mayo Clinic include: