IPSCs是指一種生物（例如小鼠或人類）細(xì)胞被重新編程后形成的類似胚胎干細(xì)胞的細(xì)胞。這類細(xì)胞有潛力按照人類的意志分化為各種類型的細(xì)胞，因此有可能使像糖尿病或帕金森癥這類的疾病得到治愈。為了弄清楚是否可以實(shí)現(xiàn)這一目的，研究人員已經(jīng)從捐贈(zèng)者身上獲取了組織細(xì)胞，并重新編程它們，之后將其注射回同一個(gè)捐贈(zèng)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(jī)體的免疫反應(yīng)，進(jìn)而導(dǎo)致這些細(xì)胞被消滅了。

在這一新研究中，來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(zèng)者的組織，重編程組織細(xì)胞并注射回捐贈(zèng)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(dāng)嵌合體長成一個(gè)組織后，再將它們注射回原來的捐贈(zèng)者體內(nèi)。他們的論文指出，這樣做并不會(huì)導(dǎo)致更多的免疫反應(yīng)。

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

這一新結(jié)果并沒有解決關(guān)于該話題的爭論，因?yàn)閮山M研究人員分別使用了不同的方法，但是該結(jié)果的發(fā)現(xiàn)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)造新組織來治愈人類各種各樣的疾病。

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.