title: Concise review: modeling multiple sclerosis with stem cell biological platforms: toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration.
abstract: 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.
authors.affiliation: 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.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Orack
authors.affiliation: 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.
authors.forename: Michela
authors.initials: M
authors.lastname: Deleidi
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Pitt
authors.affiliation: 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.
authors.forename: Kedar
authors.initials: K
authors.lastname: Mahajan
authors.affiliation: 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.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Nicholas
authors.affiliation: 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.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Boster
authors.affiliation: 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.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.affiliation: 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.
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.affiliation: 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.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Watanabe
authors.affiliation: 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 Jaime.imitola@osumc.edu.
authors.forename: Jaime
authors.initials: J
authors.lastname: Imitola
mesh_terms: D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology
keywords: Cognitive decline; Endophenotypes; Multiple sclerosis; Multiple sclerosis genetics; Neurodegeneration; Secondary progressive; Stem cells; iPSCs