Promoting remyelination through cell transplantation therapies in a model of viral-induced neurodegenerative disease.
Promoting remyelination through cell transplantation therapies in a model of viral-induced neurodegenerative disease.
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DOI：
10.1002/dvdy.24658
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Lane TE
中科院分区：
文献类型：
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作者：
Mangale V;McIntyre LL;Walsh CM;Loring JF;Lane TE
多发性硬化症（MS）是一种中枢神经系统（CNS）疾病，其特征为慢性神经炎症、脱髓鞘和轴突损伤。活化淋巴细胞和髓样细胞的浸润被认为是白质损伤和轴突病变的主要原因。美国食品药品监督管理局批准了几种疗法，这些疗法可阻止活化淋巴细胞进入中枢神经系统，从而限制复发缓解型多发性硬化症患者新病灶的形成。然而，多发性硬化症研究领域的一个重大挑战是开发有效且持久的疗法，以实现轴突保护和髓鞘再生。近年来，越来越多的证据表明，某些种类的干细胞及其衍生物似乎能够抑制神经炎症，并促进髓鞘再生和轴突完整性。用嗜神经的小鼠肝炎病毒（JHMV）的JHM株对小鼠进行颅内感染会导致免疫介导的脱髓鞘和轴突病变，这使其成为研究干细胞衍生物在诱导髓鞘再生方面治疗潜力的极佳模型。本综述简要概述了我们近期将小鼠中枢神经系统神经祖细胞和人类神经前体细胞脊髓内注射到感染JHMV的小鼠体内的研究结果。接受这些细胞的感染JHMV的小鼠显示出广泛的髓鞘再生以及轴突保留。此外，我们还讨论了与持续临床恢复相关的可能机制。
Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Several United States Food and Drug Administration-approved therapies exist that impede activated lymphocytes from entering the CNS thereby limiting new lesion formation in patients with relapse-remitting forms of MS. However, a significant challenge within the field of MS research is to develop effective and sustained therapies that allow for axonal protection and remyelination. In recent years, there has been increasing evidence that some kinds of stem cells and their derivatives seem to be able to mute neuroinflammation as well as promote remyelination and axonal integrity. Intracranial infection of mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in immune-mediated demyelination and axonopathy, making this an excellent model to interrogate the therapeutic potential of stem cell derivatives in evoking remyelination. This review provides a succinct overview of our recent findings using intraspinal injection of mouse CNS neural progenitor cells and human neural precursors into JHMV-infected mice. JHMV-infected mice receiving these cells display extensive remyelination associated with axonal sparing. In addition, we discuss possible mechanisms associated with sustained clinical recovery.