Schwann cells in the subcutaneous adipose tissue have neurogenic potential and can be used for regenerative therapies.

Schwann cells in the subcutaneous adipose tissue have neurogenic potential and can be used for regenerative therapies.
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皮下脂肪组织中的雪旺细胞具有神经原性潜力,可用于再生治疗。

DOI:
10.1126/scitranslmed.abl8753
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发表时间:
2022-05-25
影响因子:
17.1
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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由于缺乏可获得的自体神经干细胞(NSCs),神经系统疾病的干细胞治疗受到阻碍。在这项研究中,神经嵴来源的雪旺细胞被发现在小鼠和人类皮下脂肪组织(SAT)中填充神经纤维束(NFBs)。含有雪旺细胞的nfb从小鼠和人SAT中收获并体外培养。在体外培养过程中,sat衍生的雪旺细胞重塑NFBs形成神经球,并表现出神经源性分化潜力。转录谱分析表明,这些NSC特性的获得可归因于培养雪旺细胞的去分化过程。新出现的细胞群被称为SAT-NSCs,因为与体内存在的内源性雪旺细胞相比,它们具有相当独特的基因表达谱、细胞标记和分化潜力。SAT-NSCs成功移植到小鼠胃肠道,在肌层内纵向和周向迁移,分化为神经元和胶质细胞,并表现出与肠神经元表型一致的神经化学编码和钙信号传导特性。这些细胞挽救了与结肠神经节病和胃轻瘫相关的功能缺陷,表明它们作为一种治疗胃肠运动障碍的细胞疗法具有治疗潜力。SAT可以很容易地收获,并且为从成人组织中衍生自体NSCs提供了前所未有的可获得性。本研究的证据表明SAT-NSCs不是来源于间充质干细胞,而是来源于NFBs内的雪旺细胞。我们的数据描述了小鼠和人类SAT-NSCs的有效分离方法,并表明这些细胞在胃肠道运动障碍的治疗应用中具有潜力。
Stem cell therapies for nervous system disorders are hindered by a lack of accessible autologous sources of neural stem cells (NSCs). In this study, neural crest–derived Schwann cells are found to populate nerve fiber bundles (NFBs) residing in mouse and human subcutaneous adipose tissue (SAT). NFBs containing Schwann cells were harvested from mouse and human SAT and cultured in vitro. During in vitro culture, SAT-derived Schwann cells remodeled NFBs to form neurospheres and exhibited neurogenic differentiation potential. Transcriptional profiling determined that the acquisition of these NSC properties can be attributed to dedifferentiation processes in cultured Schwann cells. The emerging population of cells were termed SAT-NSCs because of their considerably distinct gene expression profile, cell markers, and differentiation potential compared to endogenous Schwann cells existing in vivo. SAT-NSCs successfully engrafted to the gastrointestinal tract of mice, migrated longitudinally and circumferentially within the muscularis, differentiated into neurons and glia, and exhibited neurochemical coding and calcium signaling properties consistent with an enteric neuronal phenotype. These cells rescued functional deficits associated with colonic aganglionosis and gastroparesis, indicating their therapeutic potential as a cell therapy for gastrointestinal dysmotility. SAT can be harvested easily and offers unprecedented accessibility for the derivation of autologous NSCs from adult tissues. Evidence from this study indicates that SAT-NSCs are not derived from mesenchymal stem cells and instead originate from Schwann cells within NFBs. Our data describe efficient isolation procedures for mouse and human SAT-NSCs and suggest that these cells have potential for therapeutic applications in gastrointestinal motility disorders.
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