Abstract：
Adipose tissue-derived stem cells (ADSCs) are a kind of stem cells with multi-directional differentiation potential, which mainly restore tissue repair function and promote cell regeneration. It can be directionally differentiated into Schwann-like cells to promote the repair of peripheral nerve injury. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the repair of nerve injury, but the underlying mechanism remains unclear, which seriously limits its further application.The study aimed to identify the molecular mechanism by which overexpression of glial cell line-derived neurotrophic factor (GDNF) facilitates the differentiation of ADSCs into Schwann cells, enhancing nerve regeneration after injury. In vitro, ADSCs overexpressing GDNF for 48 h exhibited changes in their morphology, with 80% of the cells having two or more prominences. Compared with that of ADSCs, GDNF-ADSCs exhibited increased expression of the Schwann cell marker S100, nerve damage repair-related factors.ADSC cells in normal culture and ADSC cells were overexpressing GDNF(GDNF-ADSCs) were analysed using TMT-Based Proteomic Analysis and revealed a significantly higher expression of MTA1 in GDNF-ADSCs than in control ADSCs. Hes1 expression was significantly higher in GDNF-ADSCs than in ADSCs and decreased by MTA1 silencing, along with a simultaneous decrease in the expression of S100 and nerve damage repair factors. These findings indicate that GDNF promotes the differentiation of ADSCs into Schwann cells and induces factors that accelerate peripheral nerve damage repair.
摘要：
脂肪组织源性干细胞(ADSCs)是一种具有多向分化潜能的干细胞,主要恢复组织修复功能,促进细胞再生。它可以定向分化为雪旺样细胞，促进周围神经损伤的修复。胶质细胞源性神经营养因子(GDNF)在神经损伤修复中发挥重要作用,但是潜在的机制仍然不清楚，这严重限制了它的进一步应用。本研究旨在探讨胶质细胞源性神经营养因子(GDNF)过表达促进ADSCs向雪旺细胞分化的分子机制。增强损伤后的神经再生。体外，过表达GDNF48h的ADSCs表现出形态学变化,80%的细胞有两个或更多的突出。与ADSCs相比,GDNF-ADSCs显示神经损伤修复相关因子雪旺细胞标志物S100的表达增加。使用基于TMT的蛋白质组学分析对正常培养物中的ADSC细胞和过表达GDNF的ADSC细胞(GDNF-ADSC)进行分析,并显示MTA1在GDNF-ADSC中的表达显著高于对照ADSC。GDNF-ADSCs中的Hes1表达显著高于ADSCs,MTA1沉默后Hes1表达降低,随着S100和神经损伤修复因子的表达同时降低。这些发现表明GDNF促进ADSCs分化为雪旺细胞并诱导促进周围神经损伤修复的因子。
