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

D. Penko, H. Peiris, D. Rojas-Canales, D. Mohanasundaram, C. Drogemuller, P. Coates, C. Bonder, C. Jessup

    Research output: Contribution to journalMeeting Abstractpeer-review

    Abstract

    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.
    Original languageEnglish
    Article numberC1711
    Pages (from-to)359
    Number of pages1
    JournalTransplantation
    Volume98
    Issue numberS1
    Publication statusPublished - 15 Jul 2014
    EventTransplantation Society of Australia and New Zealand 2014 - Canberra, Australia
    Duration: 11 Jun 201413 Jun 2014

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