Endothelial Progenitor Cell (EPC) Co-Transplantation Enhances the Engraftment of Pancreatic Islets and Influences Beta Cell FunctionIn Vitro.

Abstract# C1711

Islet transplantation is limited by suboptimal revascularization post-transplant. EPCs may have the potential to promote islet engraftment and improve post-transplant survival in vivo, but their mechanism of interaction with β-cells is unknown. Our aim was to assess the ability of EPCs to improve islet transplantation outcomes in a syngeneic marginal mass mouse model. C57B6 islets were isolated by Liberase^® digestion and density purification. Bone marrow-derived EPCs were enriched by culture in defined media and phenotype confirmed by flow cytometry. Diabetes was induced in C57B6 mice by streptozotocin (200mg/kg) and marginal mass of islets (200) was transplanted under the kidney capsule with or without d7 EPCs (1x10⁶ cells). Blood glucose levels (BGL) were monitored for 28d with cure defined by two consecutive BGL<11.1mM. Graft function was assessed in cured mice by intraperitoneal glucose tolerance test (IPGTT;2g/kg glucose). To assess cellular interactions, islets were cultured with EPC-conditioned medium for 3d and assayed for glucose-stimulated insulin release. Secreted insulin was measured by ELISA and corrected for total protein. EPCs expressed the endothelial marker CD31, bound lectin and took up acetylated low-density lipoprotein. Mice co-transplanted with EPCs had an improved cure rate (83% cure at d14; n=12) compared to mice receiving islets alone (20%; n=10; p=0.002). There was no significant difference in IPGTT. EPC-conditioned islets had increased basal insulin release (0.7±0.22ng/min/mg; n=7) compared to controls (0.2±0.04ng/min/mg; n=6; p=0.05). However, they had reduced ability to upregulate insulin release in high glucose conditions (SI=1.3±0.5 compared to 4.2±0.9 for controls; p<0.05). EPCs alter insulin secretion from β-cells and may improve their engraftment during pancreatic islet transplantation.