The Omentum as an Alternative Islet Transplant Site
This past year at the Diabetes Research Institute, we reached a significant milestone: several of our islet transplant patients celebrated 10 years of freedom from insulin injections, demonstrating that this cell replacement therapy can restore natural insulin production in those with type 1 diabetes.
While islet transplantation has allowed many of the patients who qualify for this experimental procedure to enjoy an increased quality of life, several challenges remain before we can offer this life-changing therapy to the millions with diabetes.
Identifying an Optimal Transplant Site
In clinical islet transplantation, the insulin-producing cells have traditionally been implanted within the liver. However, many of the cells do not survive in this environment due to several factors. Our team is working to identify an optimal site within the body to house the transplanted islets in an environment that more closely replicates the native pancreas, where the cells thrive before being destroyed by the immune system in type 1 diabetes.
The site we are currently investigating is the omentum, a highly vascularized (rich in blood vessels) tissue covering abdominal organs. The omentum is easily accessed by minimally invasive surgery, has a large surface area, and, importantly, has the same blood supply and drainage characteristics of the pancreas. We believe that the omentum may offer a more hospitable home for the transplanted cells. Encouraging preliminary results in animal models have demonstrated that islets in the omentum can engraft (become lodged in the tissue, get their own vessels and start producing insulin) and improve blood glucose control.
New Clinical Trial Underway
This work has now advanced to the clinical stage of testing. Our team at the DRI has received approval from the Food and Drug Administration (FDA) to conduct a clinical trial to test the omentum as an alternative transplant site to the liver. The identification of an alternate site is of great importance in the field, as it may translate into improved insulin independence rates and long-term graft function in patients with type 1 diabetes.
This clinical trial is also an important first step in developing the DRI BioHub, a bioengineered mini-organ to mimic the pancreas. The islets are transplanted within a fully-resorbable (biodegradable) biologic scaffold consisting of the patient’s plasma (the liquid part of the blood that does not contain cells) and human thrombin, a clotting enzyme commonly used in surgical procedures.
The biologic scaffold will serve as a platform that adheres to the omentum and holds the islets in place. The patients in this clinical trial will require the same immunosuppressive (anti-rejection) drug regimen as used in islet transplants within the liver. However, our goal at the DRI is to eliminate the need for these drugs. The development of the DRI BioHub, together with several other areas of research strategies underway at the Institute, are aimed at overcoming the challenges of the immune system.