Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells

摘要

从一个患者自己的体细胞获取的"诱导多能干rn细胞"(iPSCs)可能具有很大治疗潜力.人们rn的希望是,来自iPSC的分化细胞可避免任何rn免疫源反应.在这项研究中,Masumi Abe及rn其同事评估了从一大组同基因小鼠胚胎干细胞rn和iPSC细胞获得的皮肤和骨髓组织的免疫原性.他们获得的结果表明,主体所产生的免疫rn排斥是可以忽略不计的.%The advantages of using induced pluripotent stem cells (iPSCs) instead of embryonic stem (ES) cells in regenerative medicine centre around circumventing concerns about the ethics of using ES cells and the likelihood of immune rejection of ES-cell-derived tissues. However, partial reprogramming and genetic instabilities in iPSCs could elicit immune responses in transplant recipients even when iPSC-derived differentiated cells are transplanted. iPSCs are first differentiated into specific types of cells in vitro for subsequent transplantation. Although model transplantation experiments have been conducted using various iPSC-derived differentiated tissues and immune rejections have not been observed, careful investigation of the immunogenicity of iPSC-derived tissue is becoming increasingly critical, especially as this has not been the focus of most studies done so far. A recent study reported immunogenicity of iPSC- but not ES-cell-derived terato-mas and implicated several causative genes. Nevertheless, some controversy has arisen regarding these findings12. Here we examine the immunogenicity of differentiated skin and bone marrow tissues derived from mouse iPSCs. To ensure optimal comparison of iPSCs and ES cells, we established ten integration-free iPSC and seven ES-cell lines using an inbred mouse strain, C57BL/6. We observed no differences in the rate of success of transplantation when skin and bone marrow cells derived from iPSCs were compared with ES-cell-derived tissues. Moreover, we observed limited or no immune responses, including T-cell infiltration, for tissues derived from either iPSCs or ES cells, and no increase in the expression of the immunogenicity-causing Zg16 and Hormad1 genes in regressing skin and teratoma tissues. Our findings suggest limited immunogenicity of transplanted cells differentiated from iPSCs and ES cells.