Immunogenicity and functional evaluation of iPSC-derived organs for transplantation.
Immunogenicity and functional evaluation of iPSC-derived organs for transplantation.
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用于移植的 iPSC 衍生器官的免疫原性和功能评估
DOI：
10.1038/celldisc.2015.15
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发表时间：
2015
期刊：
影响因子：
33.5
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Wang L;Cao J;Wang Y;Lan T;Liu L;Wang W;Jin N;Gong J;Zhang C;Teng F;Yan G;Li C;Li J;Wan H;Hu B;Li W;Zhao X;Qi Z;Zhao T;Zhou Q
生理诱导多能干细胞（iPSC）来源的器官是否具有免疫原性并可用于移植尚不清楚。在这里，我们通过 4n 互补生成了代表身体三个胚层的 iPSC 来源的皮肤、胰岛和心脏，并评估了它们的免疫原性和治疗效果。移植到受体小鼠体内后，iPSC 衍生的皮肤成功存活并修复了局部组织伤口。在糖尿病小鼠模型中，移植的 iPSC 衍生胰岛可以有效产生胰岛素，并将血糖降低至基础水平。 iPSC 衍生的心脏移植物在同基因受体中保持正常跳动超过 3 个月。重要的是，移植后很长时间没有检测到针对 iPSC 衍生器官的明显免疫排斥反应。我们的研究不仅证明了 iPSC 衍生物的基本免疫原性和功能，而且还提供了临床前证据来支持使用 iPSC 衍生的皮肤、胰岛和心脏进行治疗的可行性。
Whether physiologically induced pluripotent stem cell (iPSC)-derived organs are immunogenic and can be used for transplantation is unclear. Here, we generated iPSC-derived skin, islet, and heart representing three germ layers of the body through 4n complementation and evaluated their immunogenicity and therapeutic efficacy. Upon transplantation into recipient mice, iPSC-derived skin successfully survived and repaired local tissue wounds. In diabetic mouse models, explanted iPSC-derived islets effectively produced insulin and lowered blood glucose to basal levels. iPSC-derived heart grafts maintained normal beating for more than 3 months in syngeneic recipients. Importantly, no obvious immune rejection responses against iPSC-derived organs were detected long after transplantation. Our study not only demonstrates the fundamental immunogenicity and function of iPSC derivatives, but also provides preclinical evidence to support the feasibility of using iPSC-derived skin, islet, and heart for therapeutic use.