Comparative Studies of Subcutaneous, Omental, and Portal Islet Transplantation Sites
This project addresses a bottleneck issue in cell transplant for the treatment of type 1 diabetes (T1D).
This project aims to identify an optimal site outside the liver for improved islet/stem cell transplant. We will test 2 sites: the omentum (OM, tissue around gut) and subcutaneous (SC, under the skin) in dogs.
The OM provides a large, easy-to-access area for transplant; but has poor blood supply. We will use 2 sheet designs to overcome this issue. Sheet 1 contains PVA, which has been successfully used to reverse diabetes in mice. Sheet 2 is an alginate-based sheet that protects cells between 2 layers. Transplant to the SC site is less invasive, but limitations include cell clumping, slow blood vessel growth, inflammation, and potential damage to transplanted cells because they are close to the body’s surface. A small stainless-steel mesh cage will be constructed to allow blood vessels to grow before the islet cells are placed inside. The OM sheets and SC cage will be treated with the factors to help blood vessels grow. A drug to prevent inflammation with also be tested to improve results. Results at the liver, OM and SC sites will be compared to identify the best transplant site. We will also test our stem cell’s function at the selected transplant site.
This study will address problems facing the use of cell therapy for T1D by improving cell survival and the safety of future stem cell transplants by allowing the retrieval of cells, if rejection or cancer develops.
It is estimated that 1 out of 7 California (CA) residents has diabetes or is at high risk of developing the disease. Up to 10% (300,000) are thought to have or be at risk for type 1 diabetes (T1D). T1D is an autoimmune disease that destroys insulin producing cells. Patients with T1D must take insulin injections to survive. Even with insulin, it is difficult to achieve good blood sugar control, which can lead to devastating complications, including heart disease, blindness, limb amputation, and kidney failure. A quarter of the Medicare budget is spent on diabetes-related care, which is a financial burden to State and Federal health care programs, and the taxpayers who support them.