Cotransplantation of Mesenchymal Stem Cells With Neonatal Porcine Islets Improve Graft Function in Diabetic Mice
Cotransplantation of Mesenchymal Stem Cells With Neonatal Porcine Islets Improve Graft Function in Diabetic Mice
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DOI：
10.2337/db16-1068
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发表时间：
2017-05-01
期刊：
影响因子：
7.7
通讯作者：
Korbutt, Gregory S.
中科院分区：
文献类型：
--
作者：
Hayward, Julie A.;Ellis, Cara E.;Korbutt, Gregory S.
间充质干细胞（MSC）具有免疫调节、抗炎和促血管生成的特性，因此具有改善胰岛移植和存活的潜力。我们评估了人骨髓源性MSC对体外新生猪胰岛（NPI）的影响，并确定了在小鼠模型中共同移植时的胰岛植入和代谢结果。与MSC共培养的NPI具有更高的细胞胰岛素含量，并增加葡萄糖刺激的胰岛素分泌。在糖尿病B6.129S7-Rag 1（tm 1 Mom）/J小鼠中共移植NPI与或不与MSC。监测血糖和体重，直到糖尿病逆转;然后对小鼠进行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。NPI和MSC的共移植导致显著更早的正常血糖和血管形成，改善葡萄糖耐量，并增加胰岛素含量。一项用来自自身免疫性疾病供体的MSC进行的实验对移植结果没有积极影响。人骨髓间充质干细胞与NPI的共移植表现出有益的代谢效应，可能是由于早期胰岛血管化和改善胰岛移植。此外，骨髓间充质干细胞的供体病理可影响骨髓间充质干细胞的功能能力。
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(tm1Mom)/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.