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在特定条件下从脂肪来源干细胞高效生成功能性雪旺细胞。

Efficient generation of functional Schwann cells from adipose-derived stem cells in defined conditions.

作者信息

Xie Songtao, Lu Fan, Han Juntao, Tao Ke, Wang Hongtao, Simental Alfred, Hu Dahai, Yang Hao

机构信息

a Department of Burn Surgery , Xijing Hospital, Fourth Military Medical University, Xi'an PR China State Key Laboratory of Cancer Biology, Xijing Hospital Fourth Military Medical University , Xi'an , Shaanxi Province , China.

b Department of Biochemistry and Molecular Biology , China State Key Laboratory of Cancer Biology, Fourth Military Medical University , Xi'an , Shaanxi Province , China.

出版信息

Cell Cycle. 2017 May 3;16(9):841-851. doi: 10.1080/15384101.2017.1304328. Epub 2017 Mar 15.

Abstract

Schwann cells (SCs) are hitherto regarded as the most promising candidates for viable cell-based therapy to peripheral nervous system (PNS) injuries or degenerative diseases. However, the extreme drawbacks of transplanting autologous SCs for clinical applications still represent a significant bottleneck in neural regenerative medicine, mainly owing to the need of sacrificing a functional nerve to generate autologous SCs and the nature of slow expansion of the SCs. Thus, it is of great importance to establish an alternative cell system for the generation of sufficient SCs. Here, we demonstrated that adipose-derived stem cells (ADSCs) of rat robustly give rise to morphological, phenotypic and functional SCs using an optimized protocol. After undergoing a 3-week in vitro differentiation, almost all of treated ADSCs exhibited spindle shaped morphology similar to genuine SCs and expressed SC markers GFAP and S100. Most importantly, apart from acquisition of SC antigenic and biochemical features, the ADSC-derived SCs were functionally identical to native SCs as they possess a potential ability to form myelin, and secret nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF). The current study may provide an ideal strategy for harvesting sufficient SCs for cell-based treatment of various peripheral nerve injuries or disorders.

摘要

雪旺细胞(SCs)一直被认为是外周神经系统(PNS)损伤或退行性疾病基于活细胞治疗最有前景的候选细胞。然而,自体雪旺细胞移植用于临床应用存在极大弊端,这仍然是神经再生医学的一个重大瓶颈,主要是因为需要牺牲一条功能神经来产生自体雪旺细胞,以及雪旺细胞增殖缓慢的特性。因此,建立一种替代细胞系统以产生足够的雪旺细胞至关重要。在此,我们证明,使用优化方案,大鼠脂肪来源干细胞(ADSCs)能高效分化为形态、表型和功能上的雪旺细胞。经过3周的体外分化后,几乎所有处理过的脂肪来源干细胞都呈现出与真正雪旺细胞相似的纺锤形形态,并表达雪旺细胞标志物胶质纤维酸性蛋白(GFAP)和S100。最重要的是,除了获得雪旺细胞的抗原和生化特征外,脂肪来源干细胞分化的雪旺细胞在功能上与天然雪旺细胞相同,因为它们具有形成髓鞘的潜在能力,并能分泌神经生长因子(NGF)、脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)。本研究可能为获取足够的雪旺细胞用于基于细胞的各种外周神经损伤或疾病治疗提供理想策略。

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