能量代谢触发植入干细胞和损伤视网膜细胞Graft-to Host细胞间通讯/物质交换及命运转变的机制

干细胞移植是治疗视网膜变性最有前景的治疗方法之一，已经进入临床试验阶段，但其治疗机制尚不清楚。近来发现，除了细胞替代、营养效应外，植入的干细胞及其子代细胞和受者视网膜细胞的细胞间通讯及物质交换可能是干细胞产生长期疗效的主要机制，但目前尚不清楚干细胞与不同视网膜细胞（感光细胞、视网膜色素上皮细胞和Müller细胞）产生这一作用的触发机制及其对变性细胞功能的影响。本室前期发现与干细胞融合可致体细胞重编程、干细胞通过TnT和氧化损伤的细胞进行线粒体交换而对其产生保护作用，显示干细胞和不同视网膜细胞的能量代谢差异可能是触发不同通讯方式和交换物质的决定因素。本研究拟采用氧化损伤细胞模型和视网膜损伤及变性小鼠大鼠模型，采用双光子显微成像、单细胞测序和代谢组学等方法，研究小鼠胚胎干细胞诱导视杯来源视网膜祖细胞治疗视网膜损伤的细胞通讯和物质交换机制，为阐明干细胞修复变性视网膜的新机制提供线索。

Stem cell based cell therapy is one of the most promising therapies in the treatment of retinal damage and retinal degeneration. It has been used in the clinical practice. Recently, in addition to cell replacement, trophic action, the intercellular communications fusion and organelle exchange between the grafted stem cells or their daughter cells and the retinal cells of recipient has been regarded as the major mechanism of stem cell therapy and it plays a key role in the long term therapeutic effect of stem cell, however, the underlying mechanism of the cell fusion and organelle exchange between the grafted stem cells and different cells in the retina including photoreceptor cells, retinal pigment epithelial cells and Müller cells and its influence on the damage and degenerative cells have not been clarified. Recently we found that cell fusion with stem cell causes the reprogramming of somatic cells, the mitochondrial can be transfered through tunneling nanotubes (TnT) from stem cells to oxidative stressed cells and produce protective effect, the differences in energy metabolism between stem cells and retinal cells might be a determinant of cell fusion and organelle exchange. In present study, we used oxidative stress injuried cell model of and retinal degeneration mice and rat model, and two-photon microscopy, transcriptomics and metabolomics, to explore the mechanism of cell fusion and organelle exchange of grafted human embryonic stem cells induced optic cup derived retinal progenitor cells in treatment of retinal degeneration. The result will provide a new theoretical basis for the mechanism of stem cell based cell therapy in the retinal degeneration