Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential Therapeutic Target for Myelin Repair.
Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential Therapeutic Target for Myelin Repair.
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DOI：
10.1016/j.stemcr.2017.04.011
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发表时间：
2017-06-06
影响因子：
5.9
通讯作者：
Cho YS
中科院分区：
文献类型：
--
作者：
Kim HS;Lee J;Lee DY;Kim YD;Kim JY;Lim HJ;Lim S;Cho YS
雪旺细胞通过支持轴突生长和髓鞘形成，在成功的神经修复和再生中发挥着至关重要的作用。然而，人类施万细胞的来源对于施万细胞发育和生物学的研究以及施万细胞相关疾病的治疗方法的开发都是有限的。在这里，我们提供了一种快速且可扩展的方法，利用 TGF-β 和 GSK-3 信号通路抑制剂以及神经调节蛋白-1 在化学定义的条件下联合序贯治疗 18 天，从人多能干细胞 (hPSC) 中产生自我更新的雪旺细胞前体 (SCP)。 1 周内，hPSC 衍生的 SCP 可以分化为未成熟的雪旺细胞，这些细胞的功能通过其神经营养因子的分泌及其在体外和体内的髓鞘形成能力得到了证实。我们认为，hPSC 衍生的 SCP 是一种有前途的、无限的功能性雪旺细胞来源，可用于治疗脱髓鞘疾病和周围神经系统损伤。 hPSC-SCP 在化学成分确定的培养基条件下具有高度可扩展性 hPSC-SCP 可以快速有效地分化为功能性雪旺细胞 SCP-SC 有髓鞘化轴突并分泌各种神经营养因子 SCP-SC 促进坐骨神经损伤小鼠的轴突再生 在这篇文章中，Cho 及其同事展示了一种通过成功衍生可扩展雪旺细胞前体来直接生产无限供应的功能性人类雪旺细胞 (SC) 的有效策略(SCP) 来自人类多能干细胞 (hPSC-SCP)。 hPSC-SCP (SCP-SC) 的 SC 的功能和分子特征在体外和体内均得到显示。
Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system. hPSC-SCPs are highly expandable under chemically defined medium condition hPSC-SCPs can rapidly and efficiently differentiate into functional Schwann cells SCP-SCs myelinate axon and secrete various neurotrophic factors SCP-SCs promote axonal regeneration in sciatic nerve-damaged mice In this article, Cho and colleagues show that an efficient strategy for producing directly an unlimited supply of functional human Schwann cells (SCs) via successful derivation of expandable Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSC-SCPs). Functional and molecular characteristic of SCs from hPSC-SCPs (SCP-SCs) were shown both in vitro and in vivo.