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PLoS One. 2018 Nov 12;13(11):e0206449. doi: 10.1371/journal.pone.0206449. eCollection 2018.

Improved islet recovery and efficacy through co-culture and co-transplantation of islets with human adipose-derived mesenchymal stem cells.

Gamble A1,2,3, Pawlick R1,4, Pepper AR1,2,3,4, Bruni A1,2,3,4, Adesida A2, Senior PA1,3,4,5, Korbutt GS1,2, Shapiro AMJ1,2,3,4,5.

Author information

1
Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.
2
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
3
Members of the Canadian National Transplant Research Project (CNTRP), Edmonton, AB, Canada.
4
Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada.
5
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Abstract

Islet transplantation is an established clinical procedure for select patients with type 1 diabetes and severe hypoglycemia to stabilize glycemic control. Post-transplant, substantial beta cell mass is lost, necessitating multiple donors to maintain euglycemia. A potential strategy to augment islet engraftment is the co-transplantation of islets with multipotent mesenchymal stem cells to capitalize upon their pro-angiogenic and anti-inflammatory properties. Herein, we examine the in vitro and in vivo effect of co-culturing murine islets with human adipose-derived mesenchymal stem cells (Ad-MSCs). Islets co-cultured with Ad-MSCs for 48 hours had decreased cell death, superior viability as measured by membrane integrity, improved glucose stimulated insulin secretion and reduced apoptosis compared to control islets. These observations were recapitulated with human islets, albeit tested in a limited capacity. Recipients of marginal mouse islet mass grafts, co-transplanted with Ad-MSCs without a co-culture period, did not reverse to normoglycemia as efficiently as islets alone. However, utilizing a 48-hour co-culture period, marginal mouse islets grafts with Ad-MSCs achieved a superior percent euglycemia rate when compared to islets cultured and transplanted alone. A co-culture period of human islets with human Ad-MSCs may have a clinical benefit improving engraftment outcomes.

Conflict of interest statement

The authors have declared that no competing interests exist.

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