Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Diabetes. 2017 May;66(5):1312-1321. doi: 10.2337/db16-1068. Epub 2017 Feb 28.
Mesenchymal stem cells (MSCs) possess immunoregulatory, anti-inflammatory, and proangiogenic 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 determined islet engraftment and metabolic outcomes when cotransplanted in a mouse model. NPIs cocultured with MSCs had greater cellular insulin content and increased glucose-stimulated insulin secretion. NPIs were cotransplanted with or without MSCs in diabetic B6.129S7-Rag1/J mice. Blood glucose and weight were monitored until reversal of diabetes; mice were then given an oral glucose tolerance test. Islet grafts were assessed for the degree of vascularization and total cellular insulin content. Cotransplantation 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. Cotransplantation of human MSCs with NPIs demonstrated a beneficial metabolic effect likely as a result of earlier islet vascularization and improved islet engraftment. In addition, donor pathology of MSCs can influence the functional capacity of MSCs.
间充质干细胞（MSCs）具有免疫调节、抗炎和促血管生成特性，因此有可能改善胰岛的移植和存活。我们评估了人骨髓来源的 MSCs 对新生猪胰岛（NPIs）的体外作用，并在小鼠模型中确定了共移植时胰岛的移植和代谢结果。与 MSCs 共培养的 NPIs 具有更高的细胞胰岛素含量和增加的葡萄糖刺激胰岛素分泌。NPIs 与 MSCs 共移植或不共移植到糖尿病 B6.129S7-Rag1/J 小鼠中。监测血糖和体重，直到糖尿病逆转；然后给小鼠口服葡萄糖耐量试验。评估胰岛移植物的血管化程度和总细胞胰岛素含量。NPIs 和 MSCs 的共移植导致更早的正常血糖和血管化、改善的葡萄糖耐量和增加的胰岛素含量。一项使用自身免疫疾病供体的 MSC 进行的实验对移植结果没有积极影响。NPIs 与人 MSCs 的共移植显示出有益的代谢效应，可能是由于胰岛的早期血管化和改善的胰岛移植。此外，MSCs 的供体病理学可以影响 MSCs 的功能能力。
