Nature：新研究驳斥了IPSCs容易导致免疫反应的观点

日本的研究人员将来自小鼠的诱导多能干细胞(iPSCs) 注射回与该小鼠基因完全相同的小鼠中，并指出这样做并不会引发免疫反应，这一结果与之前另一项研究的结果相矛盾。在那篇文章中，研究人员指出利用该技术会导致机体的免疫反应，进而破坏注入的细胞。这项新研究发表在Nature杂志上，研究者们将iPSCs注入一个小鼠的胚胎中，再将该小鼠的胚胎移植到与其基因完全相同的小鼠中，而后者并没有出现明显的免疫反应。

IPSCs是指一种生物（例如小鼠或人类）细胞被重新编程后形成的类似胚胎干细胞的细胞。这类细胞有潜力按照人类的意志分化为各种类型的细胞，因此有可能使像糖尿病或帕金森症这类的疾病得到治愈。为了弄清楚是否可以实现这一目的，研究人员已经从捐赠者身上获取了组织细胞，并重新编程它们，之后将其注射回同一个捐赠者。这一工作已经给了我们一些早期的希望，但是之后，加利福尼亚大学在2011年发表的一篇研究论文指出，将iPSCs注射回小鼠后会诱发机体的免疫反应，进而导致这些细胞被消灭了。

在这一新研究中，来自日本的研究小组采取了一个不同的方法。与之前取捐赠者的组织，重编程组织细胞并注射回捐赠者不同的是，他们将这些iPSCs先注射到小鼠的胚胎中，创造出嵌合体(即该生物含有不止一套遗传信息)。当嵌合体长成一个组织后，再将它们注射回原来的捐赠者体内。他们的论文指出，这样做并不会导致更多的免疫反应。

该小组的结果反驳了之前加利福尼亚大学研究人员的结论。在那篇文章中，研究人员本来希望创造一个畸胎瘤（一种类型的肿瘤）作为证据。但是当他们注射了iPSCs后，发现其遭到了机体的破坏。这一实验的失败使人们开始关注利用iPSCs作为生成新组织的方法并用以治疗人类各种疾病的可行性。

这一新结果并没有解决关于该话题的争论，因为两组研究人员分别使用了不同的方法，但是该结果的发现再次给予了科学家们希望，即iPSCs或许有天真的可以用于创造新组织来治愈人类各种各样的疾病。

doi:10.1038/nature11807
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Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells

Ryoko Araki,1, 2 Masahiro Uda,1 Yuko Hoki,1 Misato Sunayama,1 Miki Nakamura,1 Shunsuke Ando,1 Mayumi Sugiura,1 Hisashi Ideno,1, 3 Akemi Shimada,3 Akira Nifuji1, 3 & Masumi Abe1

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.