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CX3CL1 表达间充质干细胞移植对视网膜变性大鼠模型具有神经保护和免疫调节作用。

Transplantation of CX3CL1-expressing mesenchymal stem cells provides neuroprotective and immunomodulatory effects in a rat model of retinal degeneration.

机构信息

Department of Ophthalmology, First Affiliated Hospital of Fujian Medical University, Fujian Institute of Ophthalmology, Fuzhou, China.

出版信息

Ocul Immunol Inflamm. 2013 Aug;21(4):276-85. doi: 10.3109/09273948.2013.791925. Epub 2013 May 29.

DOI:10.3109/09273948.2013.791925
PMID:23718544
Abstract

PURPOSE

To investigate the neuroprotective and immunomodulatory effects of mesenchymal stem cells (MSCs) engineered to secrete CX3CL1 on the light-injured retinal structure and function.

METHODS

Normal MSCs and CX3CL1-expressing MSCs (CX3CL1-MSCs) were transplanted into the subretinal space of light-injured rats. By ERG and TUNEL methods, their rescue effect of the host retina was compared with untreated light-injured and vehicle-injected rats. Activated microglia in the retina were stained by ED-1 antibody, and Western blot was performed to quantify cytokines secreted by the retina post-transplantation.

RESULTS

ERG analysis showed better function in CX3CL1-MSC-injected group than other groups at 21 days after transplantation (p < 0.05). CX3CL1-MSCs inhibited apoptosis of the retinal cells and microglial activation. Neurotrophic factors expression in host retina that received CX3CL1-MSCs was stronger than in the retina that received normal MSCs. Conversely, the expression of proinflammatory factors was downregulated.

CONCLUSIONS

CX3CL1-MSCs subretinal transplantation may enhance protective effect against light-induced retinal degeneration.

摘要

目的

研究 CX3CL1 分泌型间充质干细胞(MSCs)对光损伤视网膜结构和功能的神经保护和免疫调节作用。

方法

将正常 MSCs 和 CX3CL1 表达型 MSCs(CX3CL1-MSCs)移植到光损伤大鼠的视网膜下腔。通过 ERG 和 TUNEL 方法,将其对宿主视网膜的挽救作用与未经处理的光损伤和载体注射大鼠进行比较。用 ED-1 抗体染色视网膜中活化的小胶质细胞,并进行 Western blot 分析以定量移植后视网膜分泌的细胞因子。

结果

移植后 21 天,ERG 分析显示 CX3CL1-MSC 注射组的功能优于其他组(p<0.05)。CX3CL1-MSCs 抑制了视网膜细胞的凋亡和小胶质细胞的激活。接受 CX3CL1-MSCs 的宿主视网膜中神经营养因子的表达强于接受正常 MSCs 的视网膜。相反,促炎因子的表达被下调。

结论

CX3CL1-MSCs 视网膜下腔移植可能增强对光诱导的视网膜变性的保护作用。

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