Myogenic progenitor cells derived from human induced pluripotent stem cell are immune‐tolerated in humanized mice,STEM CELLS Translational Medicine

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Myogenic progenitor cells derived from human induced pluripotent stem cell are immune‐tolerated in humanized mice
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-09-02 , DOI: 10.1002/sctm.19-0452
Basma Benabdallah ₁ , Cynthia Désaulniers-Langevin ₁ , Marie-Lyn Goyer ₁ , Chloé Colas ₁ , Chantale Maltais ₂ , Yuanyi Li ₁ , Jean V Guimond ₃ , Jacques P Tremblay ₂ , Elie Haddad _{1,

4} , Christian Beauséjour _{1,

5}

Affiliation

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.

中文翻译：

源自人诱导多能干细胞的肌原性祖细胞在人源化小鼠中具有免疫耐受性

目前尚不清楚免疫反应是否会影响人类诱导多能干细胞（hiPSCs）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个核细胞的过继转移或造血干细胞和人类胸腺组织的共同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。我们的研究结果表明，虽然同种异体移植物大多被拒绝并被人类 T 细胞高度浸润，但自体细胞的移植是耐受的。我们还观察到，hiPSC 衍生的肌源性祖细胞 (MPC) 在体外不被自体 T 细胞和自然杀伤细胞靶向。

更新日期：2020-09-02

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