人类胚胎干细胞微泡诱导视网膜Müller细胞分化促进视网膜再生的研究

The degeneration of retina neurons is the main cause of retinal degenerative diseases which affect a large number of people worldwide, such as Retinitis Pigmentosa. Effective therapeutic approaches that can reverse this process and restore the retina function are limited. Human embryonic stem cell derived microvesicles (hESMVs), as a cell to cell communicator, becoming a new hope for treatment of these diseases since hESMVs can release their content to target cells and change the phenotype of those cells. Our previous data showed hESMVs from H9 human embryonic stem cells contain the same pluripotent proteins and mRNAs of related transcription factors, but at a lower amount. Those hESMVs can be internalized by MIO-MI cells in vitro and induce dedifferentiation of these cells, making them potential stem cells. At the same time, in vivo study demonstrated that hESMVs induced Müller glia proliferation in mice retina after neurotoxic (NMDA) damage, and some Müller cells that proliferated post-hESMV treatment expressed markers of amacrine cell lineage. In order to further discuss the effect and molecular mechanism of hESMVs induced differentiation to photoreceptors from Müller progenitor cells, our project will use cell and molecular biology, imunocytochemistry and immunohistochemistry as well as visual electrophysiology to explore and reveal the possible molecular mechanism of retina regeneration induced by hESMVs in vitro and in vivo, providing a new direction for the treatment of retinal degenerative diseases, especially Retinitis Pigmentosa.

视网膜神经细胞的进行性退化是以视网膜色素变性为代表的不可逆致盲性眼病的主要致病机理。目前尚无有效可靠的治疗方式逆转疾病过程并恢复视功能。人类胚胎干细胞来源的微泡（hESMVs）作为细胞间通讯者，因可将其内容物传递到靶细胞并改变靶细胞表型，成为治疗该类疾病的新希望。我们前期实验结果发现，H9胚胎干细胞源hESMVs携带与同源H9细胞一致的、表达水平稍低的多潜性相关蛋白和转录因子mRNA，且能被体外培养的MIO-M1细胞内吞，引起细胞的去分化，获得“干细胞”潜能；同时，hESMVs可诱导视网膜损伤小鼠原位Müller细胞增殖且分化为无长突细胞。为进一步探讨hESMV对Müller细胞向光感受器细胞分化的作用和机制，我们将应用细胞分子生物、免疫组化和视觉电生理技术，从细胞和动物两个层面，探讨hESMVs促进视网膜组织及功能修复的潜在机制，为视网膜退行性疾病尤其是视网膜色素变性的治疗提供新的方向。