Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells.
Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells.
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DOI：
10.1016/j.stemcr.2014.06.012
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发表时间：
2014-08-12
影响因子：
5.9
通讯作者：
Fossati, Valentina
中科院分区：
文献类型：
--
作者：
Douvaras, Panagiotis;Wang, Jing;Zimmer, Matthew;Hanchuk, Stephanie;O'Bara, Melanie A.;Sadiq, Saud;Sim, Fraser J.;Goldman, James;Fossati, Valentina
多发性硬化症（MS）是一种慢性脱髓鞘疾病，病因不明，影响中枢神经系统。虽然目前的治疗主要针对免疫系统，但新的挑战是通过髓鞘再生和神经保护策略来解决进展性MS。在这里，我们开发了一个高度可重复的方案，以有效地从诱导多能干细胞（iPSCs）中获得少突胶质细胞祖细胞（OPCs）和成熟少突胶质细胞。我们的方案的关键要素包括贴壁培养，双重SMAD抑制，以及从分化开始添加类维生素a，这可以在75天内增加OLIG2祖细胞的产量和高数量的opc。此外，我们展示了从原发性进展性多发性硬化（PPMS）患者中产生的病毒和无整合的iPSCs，以及它们向少突胶质细胞的有效分化。PPMS OPCs是功能性的，正如在震颤小鼠体内髓鞘形成所证明的那样。这些结果为利用iPSCs开发自体细胞疗法提供了令人鼓舞的进展。PPMS iPSCs在体外分化为成熟的少突胶质细胞在体内从PPMS- ipsc衍生的OPCs成功形成髓鞘。在这篇文章中，Fossati和他的同事描述了一种从诱导多能干细胞分化为少突胶质细胞祖细胞（OPCs）的高效、高可重复性的分化方案。通过该方案，他们发现来自原发性进行性多发性硬化症（MS）患者的OPCs能够在shiverer小鼠模型中形成髓鞘神经元，为未来MS自体细胞移植治疗的发展提供了前提。
Multiple sclerosis (MS) is a chronic demyelinating disease of unknown etiology that affects the CNS. While current therapies are primarily directed against the immune system, the new challenge is to address progressive MS with remyelinating and neuroprotective strategies. Here, we develop a highly reproducible protocol to efficiently derive oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from induced pluripotent stem cells (iPSCs). Key elements of our protocol include adherent cultures, dual SMAD inhibition, and addition of retinoids from the beginning of differentiation, which lead to increased yields of OLIG2 progenitors and high numbers of OPCs within 75 days. Furthermore, we show the generation of viral and integration-free iPSCs from primary progressive MS (PPMS) patients and their efficient differentiation to oligodendrocytes. PPMS OPCs are functional, as demonstrated by in vivo myelination in the shiverer mouse. These results provide encouraging advances toward the development of autologous cell therapies using iPSCs. Development of a rapid, highly efficient, and robust protocol to produce O4+ hOPCs Generation of iPSCs from primary progressive MS patients Differentiation of PPMS iPSCs to mature oligodendrocytes in vitro Successful in vivo myelination from PPMS-iPSC-derived OPCs In this article, Fossati and colleagues describe an efficient and highly reproducible differentiation protocol to generate oligodendrocyte progenitor cells (OPCs) from induced pluripotent stem cells. Using this protocol, they show that OPCs from primary progressive multiple sclerosis (MS) patients are able to myelinate neurons in the shiverer mouse model, providing the premise for the development of future autologous cell transplantation therapies in MS.
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影响因子：
16.6
作者：
Patani, R.;Hollins, A. J.;Wishart, T. M.;Puddifoot, C. A.;Alvarez, S.;de Lera, A. R.;Wyllie, D. J. A.;Compston, D. A. S.;Pedersen, R. A.;Gillingwater, T. H.;Hardingham, G. E.;Allen, N. D.;Chandran, S.
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Chandran, S.
影响因子：
16.2
作者：
Novitch, BG;Wichterle, H;Sockanathan, S
通讯作者：
Sockanathan, S
影响因子：
14.8
作者：
Liu, Ying;Jiang, Peng;Deng, Wenbin
通讯作者：
Deng, Wenbin
影响因子：
14.8
作者：
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影响因子：
11.2
作者：
Hauser, Stephen L.;Chan, Jonah R.;Oksenberg, Jorge R.
通讯作者：
Oksenberg, Jorge R.