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人神经前体细胞在糖尿病视网膜病变治疗中的潜力-临床前模型。

Potential of Human Neural Precursor Cells in Diabetic Retinopathy Therapeutics - Preclinical Model.

机构信息

Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil.

Veterinary Medicine Department, Federal University of Paraná, Curitiba, Brazil.

出版信息

Curr Eye Res. 2022 Mar;47(3):450-460. doi: 10.1080/02713683.2021.2002909. Epub 2021 Dec 6.

Abstract

PURPOSE

This study aimed to evaluate a cell therapy strategy with human neural precursor cells (hNPCs) to treat diabetic retinopathy (DR) in Wistar rats induced to diabetes by injecting streptozotocin.

MATERIAL AND METHODS

The Wharton's jelly mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate to develop neurospheres and obtain the hNPCs. The animals were divided into three groups: non-diabetic (ND) n = four, diabetic without treatment (DM) n = nine, and diabetic with cell therapy (DM + hNPCs) n = nine. After 8 weeks of diabetes induction and DR characteristics installed, intravitreal injection of hNPCs (1 × 10 cell/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were conducted before and during diabetes and after cell therapy. Four weeks posttreatment, histopathological and immunohistochemistry analyses were performed.

RESULTS

The repair of the retinal structures in the treated group (DM + hNPCs) was observed by increased thickness of neuroretinal layers, especially in the ganglion cell and photoreceptor layers, higher ERG oscillatory potentials (OPs) amplitudes, and transplanted hNPCs integration into the Retinal Pigment Epithelium.

CONCLUSIONS

The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regenerating the neuroretinal tissue.

摘要

目的

本研究旨在评估一种用人神经前体细胞(hNPCs)治疗链脲佐菌素诱导糖尿病 Wistar 大鼠糖尿病性视网膜病变(DR)的细胞治疗策略。

材料和方法

分离、扩增并接种 Wharton 胶间充质干细胞(WJ-MSCs)于生物聚合物基质上以形成神经球并获得 hNPCs。将动物分为三组:非糖尿病组(ND)n = 4,未治疗糖尿病组(DM)n = 9,细胞治疗糖尿病组(DM + hNPCs)n = 9。在诱导糖尿病 8 周并出现 DR 特征后,在 DM + hNPCs 组中进行 hNPCs(1×10 细胞/µL)的玻璃体内注射。在糖尿病发生前后和细胞治疗期间进行光学相干断层扫描(OCT)和视网膜电图(ERG)评估。治疗后 4 周进行组织病理学和免疫组织化学分析。

结果

治疗组(DM + hNPCs)的视网膜结构修复表现为神经视网膜层厚度增加,特别是在节细胞和光感受器层,ERG 振荡电位(OPs)振幅更高,以及移植的 hNPCs 整合到视网膜色素上皮中。

结论

结果表明,hNPCs 通过神经保护作用减轻 DR 进展并促进视网膜修复,使其成为再生神经视网膜组织的潜在候选物。

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