Wang Jian, Zhang Wei, He Guang-Hui, Wu Bin, Chen Song
Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, China.
Int J Ophthalmol. 2018 May 18;11(5):766-772. doi: 10.18240/ijo.2018.05.08. eCollection 2018.
To investigate the effect of the overexpression of C-X-C chemokine receptor type 4 (CXCR4) on homing of mesenchymal stem cells (MSCs) and therapeutic effects of diabetic retinopathy (DR) .
MSCs were infected by lentivirus constructed with CXCR4. The expression of CXCR4 was examined by immunofluorescence, Western blot, and quantitative polymerase chain reaction. CXCR4-overexpressing MSCs were cultured to evaluate their chemotaxis, migration, and apoptotic activities. CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR. The histological structure of DR in rats was inspected by hematoxylin and eosin staining. The expression of rhodopsin, neuron-specific enolase (NSE), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α was examined by Western blot and immunohistochemical analyses.
The transduction of MSCs by lentivirus was effective, and the transduced MSCs had high expression levels of CXCR4 gene and protein. Improved migration activities were observed in CXCR4-overexpressing MSCs. Further, reduced retinal damage, upregulation of rhodopsin and NSE protein, and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs .
The homing of MSCs can be enhanced by upregulating CXCR4 levels, possibly improving histological structures of DR. CXCR4-overexpressing MSCs can be a novel strategy for treating DR.
探讨C-X-C趋化因子受体4（CXCR4）过表达对间充质干细胞（MSCs）归巢及糖尿病视网膜病变（DR）治疗效果的影响。
用构建有CXCR4的慢病毒感染MSCs。通过免疫荧光、蛋白质印迹法和定量聚合酶链反应检测CXCR4的表达。培养过表达CXCR4的MSCs以评估其趋化性、迁移和凋亡活性。将过表达CXCR4的MSCs玻璃体内注射，观察并比较其在DR小鼠模型中的作用。通过苏木精-伊红染色检查大鼠DR的组织结构。通过蛋白质印迹法和免疫组织化学分析检测视紫红质、神经元特异性烯醇化酶（NSE）以及炎性细胞因子白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α的表达。
慢病毒对MSCs的转导有效，转导后的MSCs具有高水平的CXCR4基因和蛋白表达。过表达CXCR4的MSCs迁移活性增强。此外，过表达CXCR4的MSCs中视网膜损伤减轻，视紫红质和NSE蛋白上调，炎性细胞因子IL-6和TNF-α下调。
上调CXCR4水平可增强MSCs的归巢能力，可能改善DR的组织结构。过表达CXCR4的MSCs可能是治疗DR的一种新策略。
