日本研究人員評(píng)價(jià)了將兩種不同類型的干細(xì)胞移植到小鼠耳蝸(cochlea)中的風(fēng)險(xiǎn)和療效，然后作出結(jié)論：小鼠胚胎干細(xì)胞(embryonic stem cells, ESCs)和源自成體細(xì)胞的誘導(dǎo)性多能干細(xì)胞(induced pluripotent stem cells, iPSCs)都表現(xiàn)出類似的存活和神經(jīng)分化能力,。然而，移植iPSCs到小鼠耳蝸之中存在腫瘤生長的風(fēng)險(xiǎn),?？紤]到潛在的腫瘤產(chǎn)生性質(zhì)，他們作出結(jié)論iPSC的來源是基于iPSC的療法的一種關(guān)鍵性問題,。他們的研究結(jié)果于近期發(fā)表在Cell Transplantation期刊上,。
最近的研究已表明基于干細(xì)胞的治療方法有潛力再生聽毛細(xì)胞(hair cell)和與之相關(guān)的初級(jí)聽覺神經(jīng)元(auditory primary neuron)。這些結(jié)構(gòu)是聽力所必需的,，如果存在缺陷則會(huì)導(dǎo)致極度聽力喪失和耳聾,。
研究人員注意到胚胎干細(xì)胞(ESCs)在此之前一直被視為大有希望的用于移植的細(xì)胞候選物，然而,，它們也存在免疫排斥和倫理問題,。因此，這項(xiàng)研究比較了ESCs和三種小鼠iPSC克隆細(xì)胞系的存活和神經(jīng)分化能力,。
移植4周之后,，研究人員發(fā)現(xiàn)在接受干細(xì)胞移植的大多數(shù)耳蝸中，iPSC或ESC來源的神經(jīng)元成功地存活下來,。然而依據(jù)不同的細(xì)胞系,，存活下來的細(xì)胞數(shù)量存在差異。他們注意到鑒于耳蝸非常小,，能夠移植到耳蝸中的細(xì)胞數(shù)量是有限的,。因此，存活下來的細(xì)胞數(shù)量比較低,。
他們也注意到在移植一種iPSC之后,，在一些耳蝸中畸胎瘤(teratoma)產(chǎn)生。日本京都大學(xué)醫(yī)學(xué)研究生學(xué)院耳鼻喉科研究員Takayuki Nakagawa博士說,，“據(jù)我們了解,，這是在接受細(xì)胞移植之后第一次在耳蝸記錄畸胎瘤產(chǎn)生。”
研究人員作出結(jié)論,，移植一種iPSC細(xì)胞系形成畸胎瘤表明人們需要選擇合適的iPSC細(xì)胞系來避免腫瘤形成,。他們也注意到人們需要開發(fā)出清除神經(jīng)誘導(dǎo)之后存在的未分化細(xì)胞以在內(nèi)耳中建立起安全的基于iPSC的療法。
盡管這項(xiàng)研究并沒有研究移植細(xì)胞修復(fù)聽力喪失的能力,，但是它有助于人們深入認(rèn)識(shí)移植細(xì)胞的存活能力和命運(yùn),，而且它還表明諸如細(xì)胞來源,、它們未分化的程度之類的影響因子可能影響腫瘤產(chǎn)生的風(fēng)險(xiǎn)。(生物谷：Bioon.com)
doi:
PMC:
PMID:22305181
Fates of murine pluripotent stem cell-derived neural progenitors following transplantation into mouse cochleae
Nishimura K, Nakagawa T, Sakamoto T, Ito J.
This study evaluated the tumorigenesis risk of induced pluripotent stem (iPS) cells after transplantation into the cochlea. One mouse embryonic stem (ES) cell line and three mouse iPS cell lines, one derived from adult mouse tail-tip fibroblasts (TTFs) and two from mouse embryonic fibroblasts (MEFs), were neurally induced by stromal cell-inducing activity. Before transplantation, the efficiency of neural induction and the proportion of residual undifferentiated cells were evaluated using immunocytochemistry, and no significant differences were observed in the ratios of colonies expressing βIII tubulin, nestin, or octamer (Oct)3/4. Four weeks after transplantation into the cochleae of neonatal mice, the number of surviving transplants of TTF-derived iPS cells generated by retroviral infection was significantly higher than those of MEF-derived iPS cells generated by plasmid transfection. Teratoma formation was identified in one of five cochleae transplanted with TTF-derived iPS cells. However, no significant differences were found in the cell-proliferation activity or the extent of differentiation into mature neurons among the cell lines. These findings emphasize the necessity of selecting appropriate iPS cell lines and developing methods to eliminate undifferentiated cells after neural induction, in order to establish safe iPS cell-based therapy for the inner ear.
