Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
FASEB J. 2018 Jun;32(6):3242-3253. doi: 10.1096/fj.201700991R. Epub 2018 Jan 18.
Deficient insulin secretion caused by immaturity is the predominant disadvantage of neonatal porcine islets (NPIs) when they serve as a source for islet xenotransplantation. We hypothesize that the transplantation of NPIs with a combination of mesenchymal stem cells (MSCs) can accelerate NPI maturation and improve the engraftment and function of NPIs. After indirect coculturing with monkey MSCs over 21 d, insulin secretion and the expression of regulatory genes relevant to development were assessed in NPIs. NPIs alone or in combination with allogeneic MSCs were intraportally transplanted into diabetic monkeys. Glycemic control was monitored, and graft function was evaluated. Our results suggest that MSCs benefit both the development and proliferation of NPIs in the coexisting systems in vitro and in vivo. These effects are dependent on platelet-derived growth factor receptor-α and are relevant to the inhibition of downstream target Notch1 signaling and the activation of PI3K/protein kinase B signaling.-He, S., Wang, C., Du, X., Chen, Y., Zhao, J., Tian, B., Lu, H., Zhang, Y., Liu, J., Yang, G., Li, L., Li, H., Cheng, J., Lu, Y. MSCs promote the development and improve the function of neonatal porcine islet grafts.
胰岛细胞的不成熟导致胰岛素分泌不足，这是新生猪胰岛（NPIs）作为胰岛异种移植供体的主要缺点。我们假设，将 NPIs 与间充质干细胞（MSCs）联合移植可以加速 NPIs 的成熟，并改善 NPIs 的植入和功能。经过 21 天与猴 MSCs 的间接共培养，评估了 NPIs 的胰岛素分泌和与发育相关的调节基因的表达。将单独的 NPIs 或与同种异体 MSCs 联合进行门静脉内移植到糖尿病猴体内。监测血糖控制情况，并评估移植物功能。我们的结果表明，MSCs 有利于体外和体内共存系统中 NPIs 的发育和增殖。这些作用依赖于血小板衍生生长因子受体-α，与下游靶标 Notch1 信号的抑制和 PI3K/蛋白激酶 B 信号的激活有关。-何，S.，王，C.，杜，X.，陈，Y.，赵，J.，田，B.，卢，H.，张，Y.，刘，J.，杨，G.，李，L.，李，H.，程，J.，卢，Y. MSCs 促进了新生猪胰岛移植物的发育并改善了其功能。
