Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy.
Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy.
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早期糖尿病性视网膜病中脂肪基质细胞的再生治疗潜力。
DOI：
10.1371/journal.pone.0084671
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
March KL
中科院分区：
文献类型：
--
作者：
Rajashekhar G;Ramadan A;Abburi C;Callaghan B;Traktuev DO;Evans-Molina C;Maturi R;Harris A;Kern TS;March KL
糖尿病视网膜病变（DR）是工作年龄成年人失明的主要原因。早期DR涉及炎症、血管渗漏、血管细胞凋亡和神经变性。在这项研究中，我们假设来自脂肪组织（ASC）的基质部分的细胞可以治疗性地挽救早期DR特征。链脲佐菌素（STZ）诱导的糖尿病无胸腺裸大鼠接受单次玻璃体内注射人ASC到一只眼和生理盐水到另一只眼。糖尿病发作后两个月，与盐水治疗的糖尿病眼睛相比，注射ASC后1-3周内显着改善了“B”波振幅（通过视网膜电图测量）。随后，视网膜组织病理学评价显示，与接受盐水注射的眼睛相比，接受ASC的糖尿病眼睛中视网膜血管周围的血管渗漏和凋亡细胞显著减少。此外，分子分析显示，与接受盐水的眼睛相比，接受ASC的糖尿病视网膜中炎症基因表达下调。有趣的是，发现ASC以比在接受ASC的年龄匹配的非糖尿病视网膜中所见的更高的密度定位于视网膜血管附近。在体外，ASC在高血糖应激下表现出持续的增殖和减少的凋亡。此外，与视网膜内皮细胞共培养的ASC增强内皮存活并协作形成血管网络。综上所述，我们的研究结果表明，ASC能够拯救神经视网膜从高血糖诱导的变性，导致重要的改善视觉功能。我们的临床前研究支持基于脂肪干细胞的DR治疗的转化发展，以解决视网膜毛细血管和神经变性。
Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration.
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