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Mesenchymal stem cell-derived neural progenitors attenuate proinflammatory microglial activation via paracrine

Violaine K Harris1, Derek Bishop1, Jaina Wollowitz1

  • 1Tisch Multiple Sclerosis Research Center of New York, NY 10019, USA.

Regenerative Medicine
|February 28, 2023
PubMed

Insights

Mesenchymal stem cell-derived neural progenitor cells (MSC-NPs) modulate microglia towards a beneficial state. This suggests MSC-NP therapy may target microglia for multiple sclerosis treatment.

Area of Science:

  • Neuroscience
  • Immunology
  • Regenerative Medicine

Background:

  • Multiple sclerosis (MS) is a neuroinflammatory disease.
  • Mesenchymal stem cell-derived neural progenitor cell (MSC-NP) therapy is being explored for MS.
  • The impact of MSC-NPs on microglia, key immune cells in MS, is under investigation.

Purpose of the Study:

  • To investigate the influence of MSC-NPs on microglial activation.
  • To determine if MSC-NPs can modulate microglial polarization towards a proregenerative phenotype.

Main Methods:

  • Microglia were stimulated with MSC-NP-conditioned media.
  • Quantitative PCR and ELISA were used to assess gene and protein expression.
  • Proinflammatory and proregenerative markers, as well as phagocytic activity, were measured.

Main Results:

  • MSC-NP conditioned media reduced proinflammatory markers (e.g., CCL2) and increased proregenerative markers in microglia.
  • Phagocytic activity of microglia was reduced.
  • These paracrine effects correlated with TGF-β3 expression and were blocked by TGF-β signaling inhibition.

Conclusions:

  • MSC-NPs promote a beneficial microglial polarization via secreted factors.
  • Microglia represent a potential therapeutic target for MSC-NP cell therapy in MS.
Keywords:
CCL2MSC-NPTGF-βcell therapymesenchymal stem cellmicrogliamultiple sclerosis

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