Increased Muller Cell De-Differentiation After Grafting of Retinal Stem Cell in the Sub-Retinal Space of Royal College of Surgeons Rats
Increased Muller Cell De-Differentiation After Grafting of Retinal Stem Cell in the Sub-Retinal Space of Royal College of Surgeons Rats
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DOI：
10.1089/ten.tea.2010.0649
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发表时间：
2011-10-01
影响因子：
4.1
通讯作者：
Yin, Zheng Qin
中科院分区：
文献类型：
--
作者：
Tian, Chunyu;Zhao, Tongtao;Yin, Zheng Qin
在几种脊椎动物中，Muller神经胶质能够去分化、增殖并获得祖细胞样状态以响应急性视网膜损伤或响应外源性生长因子。我们前期的研究表明，在皇家学院（RCS）大鼠退变过程中，Muller细胞可以被激活并去分化为视网膜前体细胞，尽管有限的增殖不能维持视网膜功能。我们现在报告，大鼠视网膜干细胞（rSCs）移植到RCS大鼠减缓视网膜形态学变性的进展，并防止功能中断。进一步研究发现，rSCs移植后Chx10标记的视网膜前体细胞明显增多，其中大部分主要来源于活化的Muller细胞。rSCs移植还通过产生更多的恢复素阳性光感受器来增强神经发生潜能，这被证明来自Muller胶质源性细胞。这些结果提供了证据表明，基于干细胞的治疗可能为视网膜变性的治疗提供一种新的治疗方法，并且哺乳动物视网膜中的Muller胶质细胞可以通过rSC移植被激活和去分化，并且可能具有治疗效果。
In several vertebrate classes, the Muller glia are capable of de-differentiating, proliferating, and acquiring a progenitor-like state in response to acute retinal injury or in response to exogenous growth factors. Our previous study has shown that Muller cells can be activated and de-differentiated into retinal progenitors during Royal College of Surgeons (RCS) rats' degeneration, although the limited proliferation cannot maintain retinal function. We now report that rat retinal stem cells (rSCs) transplanted into RCS rats slowed the progression of retinal morphological degeneration and prevented the functional disruption. Further, we found that retinal progenitor cells labeled with Chx10 were increased significantly after rSCs transplantation, and most of them are mainly from activated Muller cells. rSCs transplantation also enhances neurogenic potential by producing more recoverin-positive photoreceptors, which was proved coming from Muller glia-derived cells. These results provide evidence that stem cell-based therapy may offer a novel therapeutic approach for the treatment of retinal degeneration, and that Muller glia in mammalian retina can be activated and de-differentiated by rSC transplantation and may have therapeutic effects.