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人脂肪间充质干细胞移植治疗链脲佐菌素诱导糖尿病大鼠视网膜病变。

Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats.

机构信息

Department of Ophthalmology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Road Dongcheng District, Beijing, China.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2010 Oct;248(10):1415-22. doi: 10.1007/s00417-010-1384-z. Epub 2010 May 2.

Abstract

BACKGROUND

Diabetic retinopathy is a common complication of diabetes, which is caused by injury to retinal microvasculature and neurons. Mesenchymal stem cells (MSCs), which proved to have multi-linkage differentiation capacity, including endothelial cells and neurons, might be a promising cell therapy resource. The current pilot study was performed using the streptozotocin (STZ) rat model of diabetic retinopathy injected intravenously with human adipose-derived mesenchymal stem cells (AMSCs) in an effort to investigate the potency and possible therapeutic effects of AMSCs.

METHODS

Four experimental groups of Wistar rats were included in the current study: an untreated control group of STZ diabetic rats (n = 10), a normal non-diabetic control group (n = 20), an AMSC therapy group of STZ diabetic rats (n = 50), and a sham group of STZ diabetic rats (n = 50). Blood glucose levels were monitored closely. Immunofluorescence was used to study AMSC distribution and differentiation. The integrity of the blood-retinal barrier (BRB) was evaluated by Evans blue dye infusion to evaluate the therapeutic effects.

RESULTS

After 1 week of transplantation, a significant reduction in blood glucose levels was observed in the AMSC therapy group relative to the sham group. BRB integrity was also improved, as less Evans blue dye leakage was observed. Donor cells were observed in the retinas of therapy group rats, and they expressed rhodopsin and glial fibrillary acidic protein (GFAP), specific markers for photoreceptors and astrocytes, respectively.

CONCLUSIONS

Taken together, the results of the current study suggest that AMSCs may improve the integrity of the BRB in diabetic rats by differentiation into photoreceptor and glial-like cells in the retina and by reducing the blood glucose levels. Furthermore, the data presented herein provide evidence that AMSCs may serve as a promising therapeutic approach for diabetic retinopathy.

摘要

背景

糖尿病视网膜病变是糖尿病的一种常见并发症,由视网膜微血管和神经元损伤引起。间充质干细胞(MSCs)具有多向分化能力,包括内皮细胞和神经元,可能是一种有前途的细胞治疗资源。本初步研究采用链脲佐菌素(STZ)诱导的糖尿病大鼠模型,经静脉注射人脂肪间充质干细胞(AMSCs),旨在研究 AMSCs 的效力和可能的治疗效果。

方法

本研究纳入了四组 Wistar 大鼠:未治疗的 STZ 糖尿病大鼠对照组(n = 10)、正常非糖尿病对照组(n = 20)、STZ 糖尿病大鼠 AMSC 治疗组(n = 50)和 STZ 糖尿病大鼠假手术组(n = 50)。密切监测血糖水平。免疫荧光用于研究 AMSC 的分布和分化。通过 Evans 蓝染料灌注评估血视网膜屏障(BRB)的完整性,以评估治疗效果。

结果

移植后 1 周,与假手术组相比,AMSC 治疗组的血糖水平显著降低。BRB 完整性也得到改善,观察到较少的 Evans 蓝染料渗漏。在治疗组大鼠的视网膜中观察到供体细胞,并表达视紫红质和胶质纤维酸性蛋白(GFAP),分别为光感受器和星形胶质细胞的特异性标志物。

结论

综上所述,本研究结果提示 AMSCs 通过分化为视网膜中的光感受器和神经胶质样细胞,并降低血糖水平,可能改善糖尿病大鼠 BRB 的完整性。此外,本文提供的证据表明,AMSCs 可能成为糖尿病视网膜病变的一种有前途的治疗方法。

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