Orack Joshua C, Deleidi Michela, Pitt David, Mahajan Kedar, Nicholas Jacqueline A, Boster Aaron L, Racke Michael K, Comabella Manuel, Watanabe Fumihiro, Imitola Jaime
Multiple Sclerosis Center and Laboratory for Neural Stem Cells, Departments of Neurology and Neuroscience, The Ohio State University College of Medicine Wexner Medical Center, Columbus, Ohio, USA; Department of Neurodegenerative Diseases and German Center for Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Department of Neurology and Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA; Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Multiple Sclerosis Center and Laboratory for Neural Stem Cells, Departments of Neurology and Neuroscience, The Ohio State University College of Medicine Wexner Medical Center, Columbus, Ohio, USA; Department of Neurodegenerative Diseases and German Center for Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Department of Neurology and Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA; Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Stem Cells Transl Med. 2015 Mar;4(3):252-60. doi: 10.5966/sctm.2014-0133. Epub 2015 Jan 15.
In recent years, tremendous progress has been made in identifying novel mechanisms and new medications that regulate immune cell function in multiple sclerosis (MS). However, a significant unmet need is the identification of the mechanisms underlying neurodegeneration, because patients continue to manifest brain atrophy and disability despite current therapies. Neural and mesenchymal stem cells have received considerable attention as therapeutic candidates to ameliorate the disease in preclinical and phase I clinical trials. More recently, progress in somatic cell reprogramming and induced pluripotent stem cell technology has allowed the generation of human "diseased" neurons in a patient-specific setting and has provided a unique biological tool that can be used to understand the cellular and molecular mechanisms of neurodegeneration. In the present review, we discuss the application and challenges of these technologies, including the generation of neurons, oligodendrocytes, and oligodendrocyte progenitor cells (OPCs) from patients and novel stem cell and OPC cellular arrays, in the discovery of new mechanistic insights and the future development of MS reparative therapies.
近年来，在确定调节多发性硬化症（MS）中免疫细胞功能的新机制和新药物方面取得了巨大进展。然而，一个尚未得到满足的重大需求是确定神经退行性变的潜在机制，因为尽管有目前的治疗方法，患者仍表现出脑萎缩和残疾。在临床前和I期临床试验中，神经干细胞和间充质干细胞作为改善该疾病的治疗候选者受到了相当大的关注。最近，体细胞重编程和诱导多能干细胞技术的进展使得在患者特异性环境中产生人类“患病”神经元成为可能，并提供了一种独特的生物学工具，可用于了解神经退行性变的细胞和分子机制。在本综述中，我们讨论了这些技术的应用和挑战，包括从患者中生成神经元、少突胶质细胞和少突胶质细胞祖细胞（OPC）以及新型干细胞和OPC细胞阵列，以发现新的机制见解和MS修复疗法的未来发展。
