Mesenchymal stem cell-derived neural progenitors attenuate proinflammatory microglial activation via paracrine mechanisms.
Violaine K HarrisDerek BishopJaina S WollowitzGillian K CarlingAlyssa L CarlsonNicolas DaviaudSaud A SadiqPublished in: Regenerative medicine (2023)
Background: Mesenchymal stem cell-derived neural progenitor cell (MSC-NP) therapy is an experimental approach to treat multiple sclerosis. The influence of MSC-NPs on microglial activation was investigated. Methods: Microglia were stimulated in the presence of MSC-NP-conditioned media, and proinflammatory or proregenerative marker expression was assessed by quantitative PCR and ELISA. Results: Microglia stimulated in the presence of MSC-NP-conditioned media displayed reduced expression of proinflammatory markers including CCL2, increased expression of proregenerative markers and reduced phagocytic activity. The paracrine effects of MSC-NPs from multiple donors correlated with TGF-β3 gene expression and was reversed by TGF-β signaling inhibition. Conclusion: MSC-NPs promote beneficial microglial polarization through secreted factors. This study suggests that microglia are a potential therapeutic target of MSC-NP cell therapy.
Keyphrases
- inflammatory response
- cell therapy
- neuropathic pain
- poor prognosis
- gene expression
- multiple sclerosis
- mesenchymal stem cells
- lipopolysaccharide induced
- stem cells
- lps induced
- bone marrow
- transforming growth factor
- binding protein
- dna methylation
- high resolution
- epithelial mesenchymal transition
- climate change
- umbilical cord
- replacement therapy
- liver injury
- liver fibrosis
- oxide nanoparticles