Enhancing therapeutic potential: Human adipose-derived mesenchymal stem cells modified with recombinant adeno-associated virus expressing VEGF165 gene for peripheral nerve injury.

The Kaohsiung journal of medical sciences Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI:10.1002/kjm2.12875
Shuai Jiang, Bo Chen, Zhen-Yu Sun
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Abstract

This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

增强治疗潜力:用表达 VEGF165 基因的重组腺相关病毒修饰的人脂肪间充质干细胞治疗周围神经损伤。
本研究旨在探讨用携带血管内皮生长因子165(VEGF165)基因的重组腺相关病毒(rAAV)修饰的人脂肪间充质干细胞(hADSCs)对周围神经损伤(PNI)的治疗潜力。hADSCs 被分为空白组、对照组(用 rAAV 对照载体转导)和 VEGF165 组(用 rAAV VEGF165 载体转导)。随后,诱导许旺细胞分化并评估许旺细胞标记物。坐骨神经损伤小鼠模型的神经缺损部位分别注射磷酸盐缓冲液(PBS 组)、含有 hADSCs 的 PBS(hADSCs 组)、rAAV 对照载体(对照-hADSCs 组)或 rAAV VEGF165 载体(VEGF165-hADSCs 组)。通过坐骨神经功能指数(SFI)评估运动功能恢复情况,通过甲苯胺蓝染色评估神经再生情况,同时仔细检查许旺细胞标记物和神经营养因子。改造后的 hADSCs 表现出雪旺细胞分化的增强和雪旺细胞标记物 [S100 钙结合蛋白 B (S100B)、NGF 受体 (NGFR) 和胶质纤维酸性蛋白 (GFAP)] 表达的升高。与其他三组小鼠相比,VEGF165-hADSCs 组小鼠的运动功能恢复有所改善,纤维直径、轴突直径和髓鞘厚度均有所增加,远端神经节段的许旺细胞标记物(S100B、NGFR 和 GFAP)和神经营养因子(成熟脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF))的表达也有所提高。rAAV-VEGF165 修饰增强了 hADSC 在 PNI 中的潜力,促进了运动恢复和神经再生。许旺细胞标记物和神经营养因子的升高强调了治疗的益处,为神经损伤策略提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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