日本研究人員評價了將兩種不同類型的干細胞移植到小鼠耳蝸(cochlea)中的風險和療效,，然后作出結論：小鼠胚胎干細胞(embryonic stem cells, ESCs)和源自成體細胞的誘導性多能干細胞(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險,?？紤]到潛在的腫瘤產(chǎn)生性質,，他們作出結論iPSC的來源是基于iPSC的療法的一種關鍵性問題,。他們的研究結果于近期發(fā)表在Cell Transplantation期刊上。
最近的研究已表明基于干細胞的治療方法有潛力再生聽毛細胞(hair cell)和與之相關的初級聽覺神經(jīng)元(auditory primary neuron),。這些結構是聽力所必需的,，如果存在缺陷則會導致極度聽力喪失和耳聾。
研究人員注意到胚胎干細胞(ESCs)在此之前一直被視為大有希望的用于移植的細胞候選物,，然而,，它們也存在免疫排斥和倫理問題。因此，這項研究比較了ESCs和三種小鼠iPSC克隆細胞系的存活和神經(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)不同的細胞系,，存活下來的細胞數(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胞數(shù)量是有限的,。因此，存活下來的細胞數(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。日本京都大學醫(yī)學研究生學院耳鼻喉科研究員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,。”
研究人員作出結論,，移植一種iPSC細胞系形成畸胎瘤表明人們需要選擇合適的iPSC細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)誘導之后存在的未分化細胞以在內(nèi)耳中建立起安全的基于iPSC的療法,。
盡管這項研究并沒有研究移植細胞修復聽力喪失的能力,，但是它有助于人們深入認識移植細胞的存活能力和命運，而且它還表明諸如細胞來源,、它們未分化的程度之類的影響因子可能影響腫瘤產(chǎn)生的風險,。(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.
