Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Stem Cell Reports. 2017 Jun 6;8(6):1714-1726. doi: 10.1016/j.stemcr.2017.04.011. Epub 2017 May 11.
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.
许旺细胞在成功的神经修复和再生中起着至关重要的作用，它既能支持轴突生长，又能促进髓鞘形成。然而，用于研究许旺细胞发育和生物学的人类许旺细胞的来源是有限的，同时也限制了用于治疗许旺细胞相关疾病的方法的发展。在这里，我们提供了一种快速且可扩展的方法，可从人多能干细胞（hPSC）中产生自我更新的许旺细胞前体（SCP），使用 TGF-β和 GSK-3 信号通路抑制剂联合进行序贯处理，并在化学定义条件下使用神经调节蛋白 1 处理 18 天。在 1 周内，hPSC 来源的 SCP 可分化为不成熟的许旺细胞，其通过分泌神经营养因子以及在体外和体内的髓鞘形成能力得到功能确认。我们提出 hPSC 来源的 SCP 是一种有前途的、无限的功能性许旺细胞来源，可用于治疗脱髓鞘疾病和周围神经系统损伤。
