Oral Presentation 6th Australian Health and Medical Research Congress 2012

Endothelial progenitor cells (EPC) promote engraftment of transplanted pancreatic islets (#33)

Daniella Penko 1 , Daisy Mohanasundaram 2 , Darling Rojas-Canales 3 , Christopher J Drogemuller 2 , Claudine S Bonder 4 5 , P. Toby H Coates 1 2 5 , Claire F Jessup 1 5 6
  1. School of Medicine, University of Adelaide, Adelaide, SA, Australia
  2. Renal Department, Royal Adelaide Hospital, Adelaide, SA, Australia
  3. University of Pittsburgh, Pittsburgh, PA, USA
  4. Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia
  5. Centre for Stem Cell Research, Robinson Institue, Adelaide, SA, Australia
  6. Department of Human Physiology, Flinders University of SA, Adelaide, SA, Australia

In Type 1 Diabetes (T1D), insulin-producing β-cells within pancreatic islets are destroyed by the immune system. Islet transplantation is an emerging cure for T1D but success is limited by death of hypoxic β-cells early after transplantation. EPC may improve islet engraftment and graft function. Aims: To assess the potential of EPC to improve islet transplantation in a mouse model. Methods: Murine bone marrow-derived EPC were enriched by culture with endothelial growth factors on fibronectin. Pancreatic islets were isolated from mice following pancreas inflation and digestion with Liberase®. A minimal curative mass of donor islets were cotransplanted alone or with EPC under the kidney capsule of diabetic mice and function was measured by intraperitoneal glucose tolerance test (IPGTT) at d28 post-transplantation. In order to distribute EPC throughout the islet structure, an embryoid body-forming medium was used to promote the aggregation of dispersed islets and EPC into mosaic clusters in vitro. Function was assessed via glucose-stimulated insulin release (GSIS). Results: Mosaic clusters were successfully formed by d3 in culture and responded appropriately in the GSIS. Cotransplantation of islets with EPC cured 83% of animals, compared to 50% of animals transplanted with islets alone (n=4-6 per group). There was a marginal improvement in ultimate function of engrafted mass. EPC may improve the function of transplanted islets by enhancing engraftment or secreting humoral factors that support vessel formation and β-cell function.