Zhong Cuiping, Han Yu, Ma Ji, Zhang Xuan, Sun Mengning, Wang Ye, Chen Jun, Mi Wenjuan, Xu Xuehai, Qiu Jianhua
Department of Otolaryngology, Lanzhou General Hospital of People's Liberation Army, 730050 Lanzhou, China.
Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
Neurosci Lett. 2015 Mar 30;591:93-98. doi: 10.1016/j.neulet.2015.02.027. Epub 2015 Feb 12.
Cochlear progenitor cells have a limited proliferative capability, which prevents their application in treating sensorineural hearing loss. In this study, we showed that the expression of c-Myc and cyclin A2 was down-regulated during the development of cochlear tissue and CPC differentiation. Over-expression of these two genes using adenovirus transduction, significantly affected the CPC cell cycle and promoted the CPC proliferation. We further demonstrated that this promotion involves the classic CKI-cyclin-CDK pathway. Our study suggests that genetically modified CPCs may be a promising cell source for cochlear stem cell transplantation that improves the efficacy of cell therapy.
耳蜗祖细胞的增殖能力有限,这限制了它们在治疗感音神经性听力损失中的应用。在本研究中,我们发现c-Myc和细胞周期蛋白A2在耳蜗组织发育和耳蜗祖细胞分化过程中表达下调。通过腺病毒转导过表达这两个基因,显著影响了耳蜗祖细胞的细胞周期并促进了其增殖。我们进一步证明,这种促进作用涉及经典的细胞周期蛋白依赖性激酶抑制因子-细胞周期蛋白-细胞周期蛋白依赖性激酶途径。我们的研究表明,基因改造的耳蜗祖细胞可能是一种有前景的细胞来源,可用于耳蜗干细胞移植,提高细胞治疗的疗效。