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IPSCs是指一種生物（例如小鼠或人類(lèi)）細胞被重新編程后形成的類(lèi)似胚胎干細胞的細胞。這類(lèi)細胞有潛力按照人類(lèi)的意志分化為各種類(lèi)型的細胞，因此有可能使像糖尿病或帕金森癥這類(lèi)的疾病得到治愈。為了弄清楚是否可以實(shí)現這一目的，研究人員已經(jīng)從捐贈者身上獲取了組織細胞，并重新編程它們，之后將其注射回同一個(gè)捐贈者。這一工作已經(jīng)給了我們一些早期的希望，但是之后，加利福尼亞大學(xué)在2011年發(fā)表的一篇研究論文指出，將iPSCs注射回小鼠后會(huì )誘發(fā)機體的免疫反應，進(jìn)而導致這些細胞被消滅了。

在這一新研究中，來(lái)自日本的研究小組采取了一個(gè)不同的方法。與之前取捐贈者的組織，重編程組織細胞并注射回捐贈者不同的是，他們將這些iPSCs先注射到小鼠的胚胎中，創(chuàng )造出嵌合體(即該生物含有不止一套遺傳信息)。當嵌合體長(cháng)成一個(gè)組織后，再將它們注射回原來(lái)的捐贈者體內。他們的論文指出，這樣做并不會(huì )導致更多的免疫反應。

該小組的結果反駁了之前加利福尼亞大學(xué)研究人員的結論。在那篇文章中，研究人員本來(lái)希望創(chuàng )造一個(gè)畸胎瘤（一種類(lèi)型的腫瘤）作為證據。但是當他們注射了iPSCs后，發(fā)現其遭到了機體的破壞。這一實(shí)驗的失敗使人們開(kāi)始關(guān)注利用iPSCs作為生成新組織的方法并用以治療人類(lèi)各種疾病的可行性。

這一新結果并沒(méi)有解決關(guān)于該話(huà)題的爭論，因為兩組研究人員分別使用了不同的方法，但是該結果的發(fā)現再次給予了科學(xué)家們希望，即iPSCs或許有天真的可以用于創(chuàng )造新組織來(lái)治愈人類(lèi)各種各樣的疾病。

Negligible immunogenicity of terminally differentiated cells derived from induced plu**otent 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 plu**otent 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.