- Dr. Lina Lu, Principal Investigator
- Dr. Chandrashekhar Gandhi, Co-Investigator
- Dr. Nogc Thai, Co-Investigator
- University of Pittsburgh, Thomas E. Starzl Transplantation Institute, Pittsburgh, USA
- Cell-Based Capsulation: A Novel Approach for Long-Term Islet Allograft Survival
Islet cell transplantation provides a hope for cure of diabetes. However, the results of islet allograft transplantation are plagued by the following problems: 1) early graft loss due to lack of rapid revascularization in newly transplanted islets; and 2) graft destruction by the immune system.
Scientists are exploring better ways to prevent islet allograft rejection. One of the approaches is capsulation of islets with semipermeable membrane that not only blocks out the immune attack, but also allows passage of nutrients and metabolites (glucose, oxygen and insulin). However, this artificial device has limitations, including poor biocompatibility of the capsule and lack of revascularization.
Recently, we have found that co-transplantation of self-hepatic stellate cells (HSC) can effectively protect islet transplants from rejection without the requirement of immunosuppressive therapy. HSC are known to be actively involved in liver repair and regeneration by synthesizing extracellular matrix protein and secrete cytokines and growth factors. We have demonstrated that HSC are powerful killers of activated T cells, which contribute to immune tolerance. Our preliminary data show that when co-transplanted with islet allograft, HSC form a multiple-layer capsule surrounding islet grafts and markedly prolong graft survival. Thus, we hypothesize that co-transplanted HSC may form a biological barrier which support islet engraftment by secretion of growth factor and prevents allograft rejection by eliminating activated T cells.
In this proposal, we will determine the impact of HSC on specific T cell responses towards islet allograft, and ascertain the efficacy of HSC on improving islet engraftment. We will also determine the effect of HSC on islet grafts to treat type 1 diabetes. The results of these studies will lead to development of novel strategies for improving the outcome of cell transplantation, such as, cure of diabetes by successful islet transplantation.