Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions
Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions
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骨髓间充质干细胞增强自噬，有助于在缺氧和视网膜脱离条件下保护细胞
DOI：
10.1111/jcmm.15008
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发表时间：
2020-01-30
影响因子：
5.3
通讯作者：
Su, Guanfang
中科院分区：
文献类型：
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作者：
Liu, Xin;Xie, Jia'nan;Su, Guanfang
本研究旨在探讨骨髓间充质干细胞（BMSCs）对缺氧性光感受器损伤及实验性视网膜脱离的保护作用及其机制。分析缺氧661w细胞及与骨髓基质细胞共培养的细胞形态、存活率、凋亡和自噬情况。在视网膜脱离模型中，将骨髓间充质干细胞眼内移植，观察视网膜形态、外核层厚度、视紫红质表达以及视网膜细胞凋亡和自噬情况。缺氧诱导的661 w细胞凋亡明显增加，自噬水平增加，缺氧后8h达高峰。缺氧661w细胞与骨髓基质细胞共培养后，细胞形态较好，凋亡较少。自噬被抑制后，缺氧条件下661 w细胞凋亡增加，细胞活力降低，即使有移植的BMSCs存在。在移植有BMSCs的视网膜脱离眼中，视网膜ONL厚度更接近于正常视网膜的厚度。移植后，细胞凋亡显著减少，BMSC处理的视网膜中视网膜自噬被激活。早期自噬增加可促进661w细胞在缺氧应激下的存活。与BMSCs共培养保护661w细胞免受缺氧损伤，可能是由于自噬激活。在视网膜脱离模型中，BMSC移植可以显著减少感光细胞死亡并保护视网膜结构。骨髓间充质干细胞减少视网膜细胞凋亡和在移植后不久启动自噬的能力可能有助于视网膜细胞在视网膜脱离后低氧和营养限制环境中的存活。
Our study aimed to evaluate the protective role and mechanisms of bone marrow mesenchymal stem cells (BMSCs) in hypoxic photoreceptors and experimental retinal detachment. The cellular morphology, viability, apoptosis and autophagy of hypoxic 661w cells and cells cocultured with BMSCs were analysed. In retinal detachment model, BMSCs were intraocularly transplanted, and then, the retinal morphology, outer nuclear layer (ONL) thickness and rhodopsin expression were studied as well as apoptosis and autophagy of the retinal cells. The hypoxia‐induced apoptosis of 661w cells obviously increased together with autophagy levels increasing and peaking at 8 hours after hypoxia. Upon coculturing with BMSCs, hypoxic 661w cells had a better morphology and fewer apoptosis. After autophagy was inhibited, the apoptotic 661w cells under the hypoxia increased, and the cell viability was reduced, even in the presence of transplanted BMSCs. In retina‐detached eyes transplanted with BMSCs, the retinal ONL thickness was closer to that of the normal retina. After transplantation, apoptosis decreased significantly and retinal autophagy was activated in the BMSC‐treated retinas. Increased autophagy in the early stage could facilitate the survival of 661w cells under hypoxic stress. Coculturing with BMSCs protects 661w cells from hypoxic damage, possibly due to autophagy activation. In retinal detachment models, BMSC transplantation can significantly reduce photoreceptor cell death and preserve retinal structure. The capacity of BMSCs to reduce retinal cell apoptosis and to initiate autophagy shortly after transplantation may facilitate the survival of retinal cells in the low‐oxygen and nutrition‐restricted milieu after retinal detachment.