Background and Objectives To examine whether ischemic retinal ganglion cells (RGCs) will be salvaged from cell death by human adipose-derived mesenchymal stem cells (ADSCs) in an organotypic retina model. Methods and Results Deprived of arterial oxygen supply, whole mice retinas were cultured as an ex vivo organotypic cultures on an insert membrane in a 24-well plate. The therapeutic potential of ADSCs was examined by co-culture with organotypic retinas. ADSCs were seeded on top of the RGCs allowing direct contact, or at the bottom of the well, sharing the same culture media and allowing a paracrine activity. The number of surviving RGCs was assessed using Brn3a staining and confocal microscopy. Cytokine secretion of ADSCs to medium was analyzed by cytokine array. When co-cultured with ADSCs, the number of surviving RGCs was similarly significantly higher in both treatment groups compared to controls. Analysis of ADSCs cytokines secretion profile, showed secretion of anti-apoptotic and pro-proliferative cytokines (threshold＞1.4). Transplantation of ADSCs in a co-culture system with organotypic ischemic retinas resulted in RGCs recovery. Since there was no advantage to direct contact of ADSCs with RGCs, the beneficial effect seen may be related to paracrine activity of ADSCs. Conclusions These data correlated with secretion profile of ADSCs' anti-apoptotic and pro-proliferative cytokines.

中文翻译：

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脂肪来源的间充质干细胞对缺氧器官型视网膜培养中神经节细胞的再生作用。

背景和目的 在器官型视网膜模型中，研究人脂肪来源的间充质干细胞 (ADSC) 是否会挽救缺血性视网膜神经节细胞 (RGC) 免于细胞死亡。方法和结果 在动脉供氧被剥夺的情况下，将整个小鼠视网膜作为离体器官型培养物在 24 孔板的插入膜上进行培养。通过与器官型视网膜共培养来检查 ADSC 的治疗潜力。ADSC 接种在 RGC 的顶部，允许直接接触，或接种在孔的底部，共享相同的培养基并允许旁分泌活动。使用 Brn3a 染色和共聚焦显微镜评估存活的 RGC 的数量。通过细胞因子阵列分析 ADSC 向培养基中分泌的细胞因子。当与 ADSCs 共培养时，与对照组相比，两个治疗组中存活的 RGC 数量同样显着增加。ADSCs细胞因子分泌谱分析，显示抗凋亡和促增殖细胞因子的分泌（阈值＞1.4）。在具有器官型缺血性视网膜的共培养系统中移植 ADSC 导致 RGC 恢复。由于 ADSC 与 RGC 直接接触没有优势，所见的有益效果可能与 ADSC 的旁分泌活性有关。结论 这些数据与 ADSCs 的抗凋亡和促增殖细胞因子的分泌特征相关。在具有器官型缺血性视网膜的共培养系统中移植 ADSC 导致 RGC 恢复。由于 ADSC 与 RGC 直接接触没有优势，所见的有益效果可能与 ADSC 的旁分泌活性有关。结论 这些数据与 ADSCs 的抗凋亡和促增殖细胞因子的分泌特征相关。在具有器官型缺血性视网膜的共培养系统中移植 ADSC 导致 RGC 恢复。由于 ADSC 与 RGC 直接接触没有优势，所见的有益效果可能与 ADSC 的旁分泌活性有关。结论 这些数据与 ADSCs 的抗凋亡和促增殖细胞因子的分泌特征相关。