Centre de Recherche du CHU Ste-Justine, Montréal, Québec, Canada.
Centre de Recherche du CHUQ, Université Laval, Québec, Québec, Canada.
Stem Cells Transl Med. 2021 Feb;10(2):267-277. doi: 10.1002/sctm.19-0452. Epub 2020 Sep 2.
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.
目前尚不清楚免疫反应是否会影响大规模应用诱导多能干细胞（hiPSCs）衍生的细胞疗法。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生成的人源化小鼠模型。利用这些小鼠，我们评估了直接从肌肉活检或从 hiPSC 或成纤维细胞分化而来的成肌细胞在骨骼肌中的植入情况。我们的结果表明，虽然同种异体移植物大多被排斥并被大量人 T 细胞浸润，但自体细胞的植入被耐受。我们还观察到，hiPSC 衍生的成肌祖细胞（MPC）在体外不会被自体 T 细胞和自然杀伤细胞靶向。这些发现表明，我们使用的重编程和分化程序没有免疫原性，并且在有功能健全的人类免疫系统存在的情况下，hiPSC 衍生的 MPC 将被耐受。
