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Cited by 421Multiple Sclerosis Research StudiesMesenchymal stem cell researchSpinal Cord Injury Research

Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models

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Bai, Lianhua, Lennon, Donald P, Caplan, Arnold I, DeChant, Anne, Hecker, Jordan, Kranso, Janet, Zaremba, Anita, Miller, Robert H·2012·Nature Neuroscience
DOI 10.1038/nn.3109PMC PMC3427471
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Abstract

Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.

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  • HGF plays a key role in mediating MSCs-stimulated recovery of autoimmune diseases, remyelination and neural cell development, including in MS.

    “In several studies, HGF, a pleiotropic cytokine derived from cells of mesenchymal origin and whose main receptor is the transmembrane c-Met [235], [236], revealed a key role in mediating MSCs-stimulated recovery of autoimmune diseases, remyelination and neural cell development, including in MS [235], [236].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [236]

    The Results sections on EAE recovery, remyelination, and neural development show that HGF is important to the effects of MSC-conditioned medium in MS models and neurosphere cultures (page not supplied). The Discussion explicitly says that a functional role for HGF in human MS has not been defined. The paper also does not establish HGF-mediated MSC recovery across autoimmune diseases generally. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Bai, L., Lennon, D. P., Caplan, A. I., DeChant, A., Hecker, J., Kranso, J., Zaremba, A., & Miller, R. H.
Affiliations
Case Western Reserve University (US)
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2012-05-20
Volume
15
Issue
6
Pages
862-870
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.3109
PMC
PMC3427471
OpenAlex
W2143742274
Cited by
421
References
1
Citations by year
2026: 11 · 2025: 14 · 2024: 30 · 2023: 14 · 2022: 33 · 2021: 30 · 2020: 33 · 2019: 27 · 2018: 32 · 2017: 35 · 2016: 37 · 2015: 36 · 2014: 35 · 2013: 44 · 2012: 9
FWCI
28.66
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • School of Medicine, Case Western Reserve University
  • National Institute of Neurological Disorders and Stroke (R01NS030800, NS-30800)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
Keywords
hepatocyte growth factor, mesenchymal stem cells, multiple sclerosis, experimental autoimmune encephalomyelitis, remyelination, oligodendrocyte development, conditioned medium, spinal cord lesions, functional recovery
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Mice, Inbred C57BL, Multiple Sclerosis, Neurons, Oligodendroglia, Spinal Cord, Stem Cells, Blotting, Western, Culture Media, Conditioned, Hepatocyte Growth Factor, Proto-Oncogene Proteins c-met, Recovery of Function, Mesenchymal Stem Cell Transplantation, Mice, Rats, Neurogenesis, Mesenchymal Stem Cells

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