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 × 10⁶ 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.

中文翻译：

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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

摘要

目的

本研究旨在评估用人神经前体细胞 (hNPCs) 治疗通过注射链脲佐菌素诱导糖尿病的 Wistar 大鼠的糖尿病视网膜病变 (DR) 的细胞治疗策略。

材料与方法

Wharton 的果冻间充质干细胞 (WJ-MSCs) 被分离、扩增并接种到生物聚合物基质上以开发神经球并获得 hNPCs。将动物分为三组：非糖尿病 (ND) n = 4，未经治疗的糖尿病 (DM) n = 9，以及接受细胞治疗的糖尿病 (DM + hNPC) n = 9。在糖尿病诱导和 DR 特性安装 8 周后，在 DM + hNPCs 组中进行玻璃体内注射 hNPCs (1 × 10 ^{6细胞/µL)。}在糖尿病之前和期间以及细胞治疗之后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

通过增加神经视网膜层的厚度，特别是在神经节细胞和感光层中，观察到治疗组 (DM + hNPCs) 视网膜结构的修复、更高的 ERG 振荡电位 (OPs) 幅度以及移植的 hNPCs 整合到视网膜色素中上皮。

结论

结果表明，hNPCs 通过神经保护作用减少 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者。