人脐带间充质干细胞分化为毛细胞并且与听觉神经元形成突触的研究

Hearing loss is a major public health issue. There are billions of people suffering from deafness or hearing impairment. As a matter of fact，cochlear hair cell loss is one of the major causes of hearing impairment. The inability of the mammalian inner ear to regenerate lost hair cells is the major reason for the permanence of hearing loss and certain balance disorders. Many studies have been carried out in order to find an effective treatment. Recent studies in both lower vertebrates and mammals have uncovered genes and pathways important in hair cell development and have suggested ways that the sensory epithelia could be manipulated to achieve hair cell regeneration. But there are currently no treatments designed to halt or reverse the progression of hearing loss. Here，we present a stepwise guidance protocol starting with human umbilical cord mesenchymal stem cells and tissue-specific cells in three-dimensional culture，which were directed toward becoming ectoderm capable of responding to otic-inducing growth factors. Human umbilical cord mesenchymal stem cells in tissue-specific microenvironment may be able to be gradually induced to differentiate into functional hair cells. This project may provide an efficient new method of inducing differentiation of hair cells, which might be helpful for clinical drug development to treat deafness and balance dysfunction.

听力障碍是一个重要的公共健康问题，目前全球约有数十亿人患有耳聋或听力障碍。最常见的原因是内耳毛细胞的变性、坏死。目前还没有一种能够真正恢复听力的方法，因为哺乳动物的听觉毛细胞跟鸟类和低等脊椎动物的不同，哺乳动物的耳蜗毛细胞一旦损失后再生能力有限，常引起永久性的听力下降，治疗非常困难。国内外研究者做了大量的探索并且取得了一定的进展，逐渐发现了哺乳类动物内耳形态形成和毛细胞的产生是由局部的细胞间相互影响及特异的基因所调控。虽然研究者尝试通过外源性基因的诱导、促分化作用，进行成年哺乳动物的内耳毛细胞的再生和应用的研究，但都没有十分有效的方法促进毛细胞再生从而治愈耳聋患者。本课题拟采用人脐带间充质干细胞在特异的组织细胞微环境中共培养、在三维培养条件下能够被逐步诱导分化为有功能的耳蜗毛细胞。本项目可能是一种高效诱导分化毛细胞的新方法，为临床的新药研发和耳聋及平衡功能障碍患者的有效治疗带来新的希望。

内耳包含着感觉上皮，可以感受运动、重力和声音。哺乳动物潜在的不可逆的听力丧失是内耳感觉上皮不能够代替丧失的机械感受细胞或者毛细胞。人类脐带间充质组织来源的干细胞能够在体内和体外潜在的分化成间质组织例如成骨、软骨和脂肪细胞。还不清楚是否人脐带间充质干细胞（hUCMSCs）能够发育成内耳的感觉上皮。这项研究的目的是探索hUCMSCs能否分化成为内耳毛细胞样细胞，并且能够被毛细胞特异性的标志物所证实。从hUCMSCs诱导来的毛细胞样细胞显示有静纤毛状突起。而且，这些诱导来的毛细胞样细胞的电生理功能与内耳毛细胞相似。这个发现提示人脐带间充质干细胞有能力分化成为来源于非神经外胚层的内耳毛细胞样细胞，提示hUCMSCs在很多外胚层来源的器官中的组织修复和再生的潜在的能力。