Mesenchymal stem cells (MSCs) possess immuno-regulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow derived MSCs have on neonatal porcine islets (NPIs) in vitro and determine islet engraftment and metabolic outcomes when co-transplanted in a mouse model. NPIs co-cultured with MSCs had greater cellular insulin content and increased glucose stimulate insulin secretion. NPIs were co-transplanted with or without MSCs in diabetic B6.129S7-Rag1tm1Mom/J mice. Blood glucose and weight were monitored until reversal of diabetes, then mice were given an oral glucose tolerance test. Islet grafts were assessed for the degree of vascularization and total cellular insulin content. Co-transplantation of NPIs and MSCs resulted in significantly earlier normoglycemia and vascularization, improved glucose tolerance, and increased insulin content. One experiment conducted with MSCs from a donor with an autoimmune disorder had no positive effects on transplant outcomes. Co-transplantation of human MSCs with NPIs demonstrated to have a beneficial metabolic effect, likely due to earlier islet vascularization and improved islet engraftment. Additionally, donor pathology of MSCs can influence the functional capacity of MSCs.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1068/-/DC1.
- Received August 31, 2016.
- Accepted February 19, 2017.
- © 2017 by the American Diabetes Association.