Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.
Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.
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来源于人诱导多能干细胞的成肌祖细胞在人源化小鼠中是免疫耐受的。
DOI：
10.1002/sctm.19-0452
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发表时间：
2021-03
影响因子：
6
通讯作者：
Beauséjour C
中科院分区：
文献类型：
--
作者：
Benabdallah B;Désaulniers-Langevin C;Goyer ML;Colas C;Maltais C;Li Y;Guimond JV;Tremblay JP;Haddad E;Beauséjour C
目前尚不清楚免疫反应是否会影响人类诱导多能干细胞 (hiPSC) 衍生细胞疗法的大规模利用。为了回答这个问题，我们使用了通过外周血单核细胞过继转移或造血干细胞和人胸腺组织共移植产生的人源化小鼠模型。使用这些小鼠，我们评估了直接来自肌肉活检或从 hiPSC 或成纤维细胞分化而来的成肌细胞在骨骼肌中的植入。我们的结果表明，虽然同种异体移植物大多被排斥并被人类 T 细胞高度浸润，但自体细胞的植入是可以耐受的。我们还观察到，体外自体 T 细胞和自然杀伤细胞不靶向 hiPSC 衍生的肌源性祖细胞 (MPC)。这些发现表明，我们使用的重编程和分化程序不具有免疫原性，并且在有能力的人类免疫系统存在的情况下，hiPSC 衍生的 MPC 将被耐受。来自人类诱导多能干细胞或成纤维细胞的肌纤维在自体人源化小鼠模型中具有耐受性。低水平自体 T 细胞的浸润并不能预测骨骼肌植入失败。使用通过过继性外周血移植（Hu-AT）或造血干细胞和人胸腺组织共移植（Hu-BLT）产生的人源化小鼠模型，我们发现，尽管T细胞浸润水平较低，但直接源自胎儿肌肉或由人诱导多能干细胞或成纤维细胞分化而来的自体成肌细胞祖细胞的移植并未被排斥。
It is still unclear if immune responses will compromise the large‐scale utilization of human induced pluripotent stem cells (hiPSCs)‐derived cell therapies. To answer this question, we used humanized mouse models generated by the adoptive transfer of peripheral blood mononuclear cells or the cotransplantation of hematopoietic stem cells and human thymic tissue. Using these mice, we evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or differentiated from hiPSCs or fibroblasts. Our results showed that while allogeneic grafts were mostly rejected and highly infiltrated with human T cells, engraftment of autologous cells was tolerated. We also observed that hiPSC‐derived myogenic progenitor cells (MPCs) are not targeted by autologous T cells and natural killer cells in vitro. These findings suggest that the reprogramming and differentiation procedures we used are not immunogenic and that hiPSC‐derived MPCs will be tolerated in the presence of a competent human immune system. Myofibers derived from human induced pluripotent stem cell or fibroblasts are tolerated in autologous humanized mouse models. Infiltration of low‐level autologous T cells is not predictive of skeletal muscle engraftment failure. Using humanized mouse models generated by the adoptive transfer of peripheral blood (Hu‐AT) or the cotransplantation of hematopoietic stem cells and human thymic tissue (Hu‐BLT), we show that the transplantation of autologous myoblast progenitor cells either derived directly from fetal muscle or differentiated from human induced pluripotent stem cells or fibroblasts were not rejected despite low level T cells infiltration.
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影响因子：
8.8
作者：
Emborg ME;Liu Y;Xi J;Zhang X;Yin Y;Lu J;Joers V;Swanson C;Holden JE;Zhang SC
通讯作者：
Zhang SC
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影响因子：
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作者：
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作者：
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Takahashi, Jun
影响因子：
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作者：
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