Mechanisms of Wharton's Jelly-derived MSCs in enhancing peripheral nerve regeneration.

Mechanisms of Wharton's Jelly-derived MSCs in enhancing peripheral nerve regeneration.
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DOI:
10.1038/s41598-023-48495-6
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发表时间:
2023-12-01
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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Warton’s骨髓间充质干细胞(WJ-MSCs)在促进无细胞神经移植物(ANG)的神经再生中起着关键作用;然而,WJ-MSCs相关神经再生的机制仍不清楚。本研究通过检测WJ-MSCs的免疫调节和旁分泌作用以及分化潜能,探讨了WJ-MSCs如何促进周围神经再生。为此,从脐带中分离WJ-MSCs,并将ANG(对照)或负载WJ-MSCs的ANG(WJ-MSCs组)移植到损伤动物模型中。术后16周通过踝关节角度和强直力测量评估功能恢复。移植后3、7和14天的组织活检用于通过定量实时聚合酶链反应(RT-qPCR)和免疫荧光染色分析巨噬细胞标志物和白细胞介素(IL)水平、旁分泌效应和MSC分化潜能。与对照组相比,WJ-MSCs组在4周时踝关节角度显著增加,在16周时等长强直力显著增加,在7 d和14 d时CD 206和IL 10的表达显著增加。在第14天观察到神经营养因子和血管生长因子水平增加。WJ-MSCs组显示出较高的S100β表达水平;然而,人细胞核的共染色较弱。这项研究表明,WJ-MSCs的免疫调节和旁分泌作用有助于周围神经再生超过其分化潜力。
Warton’s jelly-derived Mesenchymal stem cells (WJ-MSCs) play key roles in improving nerve regeneration in acellular nerve grafts (ANGs); however, the mechanism of WJ-MSCs-related nerve regeneration remains unclear. This study investigated how WJ-MSCs contribute to peripheral nerve regeneration by examining immunomodulatory and paracrine effects, and differentiation potential. To this end, WJ-MSCs were isolated from umbilical cords, and ANGs (control) or WJ-MSCs-loaded ANGs (WJ-MSCs group) were transplanted in injury animal model. Functional recovery was evaluated by ankle angle and tetanic force measurements up to 16 weeks post-surgery. Tissue biopsies at 3, 7, and 14 days post-transplantation were used to analyze macrophage markers and interleukin (IL) levels, paracrine effects, and MSC differentiation potential by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The WJ-MSCs group showed significantly higher ankle angle at 4 weeks and higher isometric tetanic force at 16 weeks, and increased expression of CD206 and IL10 at 7 or 14 days than the control group. Increased levels of neurotrophic and vascular growth factors were observed at 14 days. The WJ-MSCs group showed higher expression levels of S100β; however, the co-staining of human nuclei was faint. This study demonstrates that WJ-MSCs' immunomodulation and paracrine actions contribute to peripheral nerve regeneration more than their differentiation potential.
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