Recent achievements in stem cell-mediated myelin repair

Jadasz, Janusz J.; Lubetzki, Catherine; Zalc, Bernard; Stankoff, Bruno; Hartung, Hans‐Peter; Küry, Patrick

doi:10.1097/wco.0000000000000323

Cited by 6 publications

(3 citation statements)

References 110 publications

(87 reference statements)

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“…In contrast to rat neural stem cells, human NSC differentiation into oligodendrocytes appears to be impaired and delayed (Jadasz et al, ) indicating that research efforts should be dedicated to the derivation of improved new protocols for iPSC‐derived oligodendrocyte generation. To study possible MSC dependent pro‐oligodendroglial effects in a purely human system, i.e., responses of human neural stem cells following supply of human fetal mesenchymal stem cell secreted factors, we stimulated human iPSC‐derived NSCs with H37 MSC‐CM.…”

Section: Resultsmentioning

confidence: 99%

“…Our findings unraveled a certain degree of heterogeneity among myelin repair mediating cells when it comes to intrinsic regulators and mechanisms but at the same time showed a remarkable stability of potent exogenous stimuli acting across species. Based on their immunomodulatory actions, systemic application of mesenchymal stem cells is currently under investigation in clinical trials (Jadasz et al, ; Oh et al, ). However, for a prospective biomedical translation, it would be desirable that active pro‐oligodendrogenic and anti‐astrocytic components are identified first and then applied specifically—a strategy to which our here described findings might contribute.…”

Section: Discussionmentioning

confidence: 99%

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Human mesenchymal factors induce rat hippocampal‐ and human neural stem cell dependent oligodendrogenesis

Jadasz

Tepe

Beyer

et al. 2017

Glia

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The generation of new oligodendrocytes is essential for adult brain repair in diseases such as multiple sclerosis. We previously identified the multifunctional p57kip2 protein as a negative regulator of myelinating glial cell differentiation and as an intrinsic switch of glial fate decision in adult neural stem cells (aNSCs). In oligodendroglial precursor cells (OPCs), p57kip2 protein nuclear exclusion was recently found to be rate limiting for differentiation to proceed. Furthermore, stimulation with mesenchymal stem cell (MSC)-derived factors enhanced oligodendrogenesis by yet unknown mechanisms. To elucidate this instructive interaction, we investigated to what degree MSC secreted factors are species dependent, whether hippocampal aNSCs respond equally well to such stimuli, whether apart from oligodendroglial differentiation also tissue integration and axonal wrapping can be promoted and whether the oligodendrogenic effect involved subcellular translocation of p57kip2. We found that CC1 positive oligodendrocytes within the hilus express nuclear p57kip2 protein and that MSC dependent stimulation of cultured hippocampal aNSCs was not accompanied by nuclear p57kip2 exclusion as observed for parenchymal OPCs after spontaneous differentiation. Stimulation with human MSC factors was observed to equally promote rat stem cell oligodendrogenesis, axonal wrapping and tissue integration. As forced nuclear shuttling of p57kip2 led to decreased CNPase-but elevated GFAP expression levels, this indicates heterogenic oligodendroglial mechanisms occurring between OPCs and aNSCs. We also show for the first time that dominant pro-oligodendroglial factors derived from human fetal MSCs can instruct human induced pluripotent stem cell-derived NSCs to differentiate into O4 positive oligodendrocytes.heterogeneity, inhibitors, intracellular protein shuttling, multiple sclerosis, myelin repair, neuroregeneration, oligodendrocyte Glia. 2018;66:145-160.wileyonlinelibrary.com/journal/glia

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human mesenchymal factors induce rat hippocampal‐ and human neural stem cell dependent oligodendrogenesis

Jadasz

Tepe

Beyer

et al. 2017

Glia

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“…In AHSCT, the dysregulated immune system of a patient is eliminated by chemotherapy whereupon previously isolated HSCs from the patient’s bone marrow are transplanted to generate a new immune system. Injection of MSCs, also derived from the patient’s bone marrow, is related to the many beneficial and regenerative effects that could be attributed to these cells [54,55]. While both treatments have yielded rather positive results [56], clinical trials so far have been preliminary and included low patient numbers only.…”

Section: Endogenous Versus Exogenous Stem Cell-mediated Repairmentioning

confidence: 99%

Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?

Akkermann

Jadasz

Azim

et al. 2016

IJMS

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Irreversible functional deficits in multiple sclerosis (MS) are directly correlated to axonal damage and loss. Neurodegeneration results from immune-mediated destruction of myelin sheaths and subsequent axonal demyelination. Importantly, oligodendrocytes, the myelinating glial cells of the central nervous system, can be replaced to some extent to generate new myelin sheaths. This endogenous regeneration capacity has so far mainly been attributed to the activation and recruitment of resident oligodendroglial precursor cells. As this self-repair process is limited and increasingly fails while MS progresses, much interest has evolved regarding the development of remyelination-promoting strategies and the presence of alternative cell types, which can also contribute to the restoration of myelin sheaths. The adult brain comprises at least two neurogenic niches harboring life-long adult neural stem cells (NSCs). An increasing number of investigations are beginning to shed light on these cells under pathological conditions and revealed a significant potential of NSCs to contribute to myelin repair activities. In this review, these emerging investigations are discussed with respect to the importance of stimulating endogenous repair mechanisms from germinal sources. Moreover, we present key findings of NSC-derived oligodendroglial progeny, including a comprehensive overview of factors and mechanisms involved in this process.

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Human Umbilical Cord–derived Mesenchymal Stem Cells into Oligodendrocyte-like Cells using Triiodothyronine as an Inducer: a Rapid and Efficient Protocol

Almasi-Turk

Hamidabadi

Farzadinia

et al. 2023

Regen. Eng. Transl. Med.

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Recent achievements in stem cell-mediated myelin repair

Abstract: This review summarizes recent developments and findings related to pharmacological myelin repair as well as to the modulation/application of stem cells with the aim to restore defective myelin sheaths.

Cited by 6 publications

References 110 publications

Human mesenchymal factors induce rat hippocampal‐ and human neural stem cell dependent oligodendrogenesis

Human mesenchymal factors induce rat hippocampal‐ and human neural stem cell dependent oligodendrogenesis

Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?

Human Umbilical Cord–derived Mesenchymal Stem Cells into Oligodendrocyte-like Cells using Triiodothyronine as an Inducer: a Rapid and Efficient Protocol

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