Stem cell derived oligodendrocytes to study myelin diseases

Chanoumidou, Konstantina; Mozafari, Sabah; Evercooren, Anne Baron-Van; Kuhlmann, Tanja

doi:10.1002/glia.23733

Cited by 49 publications

(43 citation statements)

References 123 publications

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“…We observed only a very low percentage of proliferating OPC in these lesions suggesting that these cells may not be major contributors to remyelination. Considering further the fact that OPC account for approximately 5% of the total oligodendroglial population and the relatively long time period required for differentiation of human OPC into mature oligodendrocytes [ 7 , 12 , 39 ], it appears unlikely that only recently differentiated OPC contributed to successful remyelination in active/demyelinating lesions, but instead favors a scenario in which also mature oligodendrocytes surviving the initial inflammatory attack contribute to remyelination. However, one has to keep in mind that Ki-67 only identifies cells which are actively dividing.…”

Section: Discussionmentioning

confidence: 99%

Lesion stage-dependent causes for impaired remyelination in MS

et al. 2020

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Multiple sclerosis (MS) is the most frequent demyelinating disease and a leading cause for disability in young adults. Despite significant advances in immunotherapies in recent years, disease progression still cannot be prevented. Remyelination, meaning the formation of new myelin sheaths after a demyelinating event, can fail in MS lesions. Impaired differentiation of progenitor cells into myelinating oligodendrocytes may contribute to remyelination failure and, therefore, the development of pharmacological approaches which promote oligodendroglial differentiation and by that remyelination, represents a promising new treatment approach. However, this generally accepted concept has been challenged recently. To further understand mechanisms contributing to remyelination failure in MS, we combined detailed histological analyses assessing oligodendroglial cell numbers, presence of remyelination as well as the inflammatory environment in different MS lesion types in white matter with in vitro experiments using induced-pluripotent stem cell (iPSC)-derived oligodendrocytes (hiOL) and supernatants from polarized human microglia. Our findings suggest that there are multiple reasons for remyelination failure in MS which are dependent on lesion stage. These include lack of myelin sheath formation despite the presence of mature oligodendrocytes in a subset of active lesions as well as oligodendroglial loss and a hostile tissue environment in mixed active/inactive lesions. Therefore, we conclude that better in vivo and in vitro models which mimic the pathological hallmarks of the different MS lesion types are required for the successful development of remyelination promoting drugs.

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Section: Discussionmentioning

confidence: 99%

Lesion stage-dependent causes for impaired remyelination in MS

et al. 2020

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“…Although the biology of oligodendroglial cells is conserved between rodents and humans, there are some differences between species that should be considered for any translation from murine models to the human physiology (reviewed in [136,137]). The peculiar structure and position of the brain and spinal cord reduces the possibilities of obtaining cells directly from human CNS tissue.…”

Section: Models To Study Oligodendrocytes and Opcmentioning

confidence: 99%

Oligodendrocytes in Development, Myelin Generation and Beyond

Kuhn

Gritti

Crooks

et al. 2019

Cells

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Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.

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“…Technically, and similar to the case with neurons, two different strategies are available to generate hiPSC-derived oligodendrocyte progenitor cells/oligodendrocytes (for details, we refer the reader to detailed reviews [103,104]). The first and older strategy is to mimic the embryological and "natural" development of oligodendrocyte progenitor cells/oligodendrocytes by in vitro patterning with chemical stimulation.…”

Section: Patient-derived Neurobiological Test Systems Indicate Oligodmentioning

confidence: 99%

Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

Raabe

Slapakova

Rossner

et al. 2019

Cells

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Imaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity. Oligodendrocyte precursors form a synaptic network with parvalbuminergic interneurons, and disturbed crosstalk between these cells may be a cellular basis of pathology in schizophrenia. However, very little is known about the exact axon-glial cellular and molecular processes that may be disturbed in schizophrenia. Until now, investigations were restricted to peripheral tissues, such as blood, correlative imaging studies, genetics, and molecular and histological analyses of postmortem brain samples. The advent of human-induced pluripotent stem cells (hiPSCs) will enable functional analysis in patient-derived living cells and holds great potential for understanding the molecular mechanisms of disturbed oligodendroglial function in schizophrenia. Targeting such mechanisms may contribute to new treatment strategies for previously treatment-resistant cognitive symptoms.

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Stem cell derived oligodendrocytes to study myelin diseases

Cited by 49 publications

References 123 publications

Lesion stage-dependent causes for impaired remyelination in MS

Lesion stage-dependent causes for impaired remyelination in MS

Oligodendrocytes in Development, Myelin Generation and Beyond

Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

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