Research Group

  • Dr. Juan Contreras, Principal Investigator
  • Dr. Devin Eckhoff, Co-Investigator
  • Ms. Cheryl Smyth, Research Associate

Location

  • University of Alabama, Birmingham, USA

Title

  • Increase of Islet Engraftment by Mobilizing Bone-Marrow-Derived Endothelial Progenitor Cells

Pancreatic islet transplantation (PIT) has been validated as a treatment for human type I insulin-dependent diabetes mellitus (IDDM). However, in the most successful clinical experience in PIT, two or more islet infusions were necessary to achieve sufficient engrafted islet mass for establishing normoglycemia without exogenous insulin therapy. While islet re-transplantation is effective, it lacks cost-effectiveness and is constrained by the shortfall of donor pancreatic tissue. Thus, new strategies for improving durable functional islet mass will be instrumental in facilitating PIT as a cure for IDDM. When islets are isolated and cultured before transplantation, the islet endothelium dedifferentiates or degenerates. A rapid revascularization is therefore crucial for islet function and engraftment after transplantation. Recent studies demonstrated that the vascular density in revascularized transplanted islets is markedly decreased compared with endogenous islets. The feasibility of revascularization of ischemic tissues by mobilizing bone-marrow endothelial progenitor cells (angioblasts) or transplantation of ex vivo expanded angioblasts has been demonstrated. Therefore, the long-term objective of this proposal is to evaluate the possibility of increasing islet revascularization and therefore preserving functional islet mass after islet transplantation by mobilizing or infusing angioblasts in combination with islet transplantation. Based on these considerations, we hypothesize that mobilized or infused angioblasts can increase revascularization and engraftment of pancreatic islets. The proposed studies are innovative and likely to yield important new information and new protocols to allow implementation of PIT as a routine therapy for diabetes.