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用于视网膜血管损伤的人骨髓间充质干细胞

Human bone marrow mesenchymal stem cells for retinal vascular injury.

作者信息

Wang Jin-Da, An Ying, Zhang Jing-Shang, Wan Xiu-Hua, Jonas Jost B, Xu Liang, Zhang Wei

机构信息

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.

Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Seegartenklinik, Heidelberg, Germany.

出版信息

Acta Ophthalmol. 2017 Sep;95(6):e453-e461. doi: 10.1111/aos.13154. Epub 2016 Nov 3.

Abstract

PURPOSE

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage.

METHODS

Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count.

RESULTS

In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36).

CONCLUSIONS

Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders.

摘要

目的

研究玻璃体内植入人骨髓间充质干细胞(BMSCs)对氧诱导性视网膜病变、糖尿病性视网膜病变或视网膜缺血再灌注损伤的小鼠和大鼠的血管修复及血视网膜屏障的影响。

方法

三个研究组(氧诱导性视网膜病变组:18只C57BL/6J小鼠;糖尿病性视网膜病变组:15只大鼠;视网膜缺血再灌注模型组:18只大鼠)接受玻璃体内注射BMSCs。对照组(氧诱导性视网膜病变组:12只C57BL/6J小鼠;糖尿病性视网膜病变组:15只大鼠;视网膜缺血再灌注模型组:18只大鼠)接受玻璃体内注射磷酸盐缓冲盐水。我们应用免疫组织学技术测量视网膜血管生成,通过光谱测量视网膜内渗出的荧光素偶联葡聚糖来量化血视网膜屏障破坏,并采用组织形态计量学评估视网膜厚度和视网膜神经节细胞计数。

结果

在氧诱导性视网膜病变模型中,与对照组相比,玻璃体内注射BMSCs的研究组视网膜新生血管面积显著更小(p = 0.001)。在糖尿病性视网膜病变模型中,研究组和对照组视网膜内渗出的葡聚糖量无显著差异。在视网膜缺血再灌注模型中,视网膜损伤后第7天,研究组视网膜明显比对照组厚(p = 0.02),视网膜神经节细胞计数无显著差异(p = 0.36)。

结论

玻璃体内植入人BMSCs与氧诱导性视网膜病变模型中视网膜新生血管减少以及视网膜缺血再灌注模型中潜在的细胞保护作用相关。玻璃体内注射BMSCs可能对视网膜血管疾病的治疗具有潜在意义。

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