A central goal in beta cell biology and diabetes is the development of methods to enhance the number of beta cells that are available for cell replacement therapy, whether derived from cell lines, stem cells, cadaver or living donors. We have shown, using both using multiple in vivo approaches, that HGF markedly and consistently increases the rate of beta cell growth, potently enhances beta cell survival, and markedly improves glucose sensing and insulin secretion by beta cells. For example, mouse and rat islets transduced to overexpress HGF dramatically outperform normal islets in marginal mass islet transplant systems and in transgenic systems. The Dong group (Dr. Henry Dong at Children’s Hospital of Pittsburgh) has demonstrated that the same is true for VEGF. This is an Innovative Partnership grant filed in conjunction with a second grant by Dr. Dong. We will compare the effects of HGF delivery, either alone or in combination with VEGF, to control murine islets in a renal transplant model. Outcome measures will be: 1) defining the minimal number (mass) of islets required to induce normal bllod glucose when using control islets, islets expressing HGF alone, to islets expressing VEGF alone, and to HGF- + VEGF-expressing islets. We will also assess rates of beta cell proliferation, cell death, islet mass, and islet blood and blood vessel supply.
|Effective start/end date||1/11/05 → 31/10/06|
- Juvenile Diabetes Research Foundation United States of America: $110,000.00