Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Nature. 2013 Feb 7;494(7435):100-4. doi: 10.1038/nature11807. Epub 2013 Jan 9.
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 teratomas and implicated several causative genes. Nevertheless, some controversy has arisen regarding these findings. 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.
使用诱导多能干细胞(iPSC)代替胚胎干细胞(ES 细胞)在再生医学中的优势在于规避使用 ES 细胞的伦理问题以及 ES 细胞衍生组织免疫排斥的可能性。然而,iPSC 的部分重编程和遗传不稳定性即使在移植 iPSC 衍生的分化细胞时也可能引发移植受者的免疫反应。iPSC 首先在体外分化为特定类型的细胞,然后进行后续移植。虽然已经使用各种 iPSC 衍生的分化组织进行了模型移植实验,并且没有观察到免疫排斥,但对 iPSC 衍生组织的免疫原性进行仔细研究变得越来越重要,尤其是因为这并不是迄今为止大多数研究的重点。最近的一项研究报告了 iPSC 而不是 ES 细胞衍生的畸胎瘤的免疫原性,并涉及几个致病基因。然而,对于这些发现,存在一些争议。在这里,我们研究了来自小鼠 iPSC 的分化皮肤和骨髓组织的免疫原性。为了确保 iPSC 和 ES 细胞的最佳比较,我们使用近交系 C57BL/6 建立了十个无整合 iPSC 和七个 ES 细胞系。当比较 iPSC 和 ES 细胞衍生的组织时,我们观察到来自 iPSC 的皮肤和骨髓细胞的移植成功率没有差异。此外,我们观察到来自 iPSC 或 ES 细胞的组织的免疫反应有限或不存在,包括 T 细胞浸润,并且在消退的皮肤和畸胎瘤组织中,免疫原性引起的 Zg16 和 Hormad1 基因的表达没有增加。我们的研究结果表明,来自 iPSC 和 ES 细胞的分化细胞的免疫原性有限。