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首页 » 干细胞&iPS » Cell Transplant.:干细胞移植到小鼠耳蜗有望治疗听力丧失

Cell Transplant.:干细胞移植到小鼠耳蜗有望治疗听力丧失

来源:生物谷 2012-07-15 23:11

日本研究人员评价了将两种不同类型的干细胞移植到小鼠耳蜗(cochlea)中的风险和疗效,然后作出结论:小鼠胚胎干细胞(embryonic stem cells, ESCs)和源自成体细胞的诱导性多能干细胞(induced pluripotent stem cells, iPSCs)都表现出类似的存活和神经分化能力。然而,移植iPSCs到小鼠耳蜗之中存在肿瘤生长的风险。考虑到潜在的肿瘤产生性质,他们作出结论iPSC的来源是基于iPSC的疗法的一种关键性问题。他们的研究结果于近期发表在Cell Transplantation期刊上。

最近的研究已表明基于干细胞的治疗方法有潜力再生听毛细胞(hair cell)和与之相关的初级听觉神经元(auditory primary neuron)。这些结构是听力所必需的,如果存在缺陷则会导致极度听力丧失和耳聋。

研究人员注意到胚胎干细胞(ESCs)在此之前一直被视为大有希望的用于移植的细胞候选物,然而,它们也存在免疫排斥和伦理问题。因此,这项研究比较了ESCs和三种小鼠iPSC克隆细胞系的存活和神经分化能力。

移植4周之后,研究人员发现在接受干细胞移植的大多数耳蜗中,iPSC或ESC来源的神经元成功地存活下来。然而依据不同的细胞系,存活下来的细胞数量存在差异。他们注意到鉴于耳蜗非常小,能够移植到耳蜗中的细胞数量是有限的。因此,存活下来的细胞数量比较低。

他们也注意到在移植一种iPSC之后,在一些耳蜗中畸胎瘤(teratoma)产生。日本京都大学医学研究生学院耳鼻喉科研究员Takayuki Nakagawa博士说,“据我们了解,这是在接受细胞移植之后第一次在耳蜗记录畸胎瘤产生。”

研究人员作出结论,移植一种iPSC细胞系形成畸胎瘤表明人们需要选择合适的iPSC细胞系来避免肿瘤形成。他们也注意到人们需要开发出清除神经诱导之后存在的未分化细胞以在内耳中建立起安全的基于iPSC的疗法。

尽管这项研究并没有研究移植细胞修复听力丧失的能力,但是它有助于人们深入认识移植细胞的存活能力和命运,而且它还表明诸如细胞来源、它们未分化的程度之类的影响因子可能影响肿瘤产生的风险。(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.

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