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Updated: May 12, 2026
Adipose-Derived Mesenchymal Stromal Cells Co-Cultured with Primary Mixed Glia to Reduce Prion-Induced Inflammation
Published on: August 11, 2023
Comparative effects of bone marrow mesenchymal stem cells on lipopolysaccharide-induced microglial activation
Fan-Wei Tseng1, May-Jywan Tsai, Li-Yu Yu
1Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Abstract:
After injury to the CNS, microglia are rapidly activated and concentrated and trigger inflammatory reaction at the sites of injury. Bone marrow mesenchymal stem cells (BMMSC) represent attractive cell sources for treating CNS injury. Although anti-inflammatory and paracrine effects of grafted BMMSC have been shown, direct modulation of BMMSC on microglia in situ remains unclear. The present work employs in vitro transwell assay to characterize the effects of BMMSC on LPS-stimulated microglia. BMMSC are cultivated in serum and serum-free (sf) conditions, namely, BMMSC and BMMSC-sf. Both cultures express major surface markers specific for mesenchymal stem cells. However, the BMMSC-sf exhibit sphere-like structure with reduced expression of two adherent cell markers, CD29 and CD90. Compared to BMMSC-sf, BMMSC are fibroblast like and have faster differentiation potential into neural-like cells. Furthermore, BMMSC release significant levels of TIMP-1 and VEGF, regardless of being alone or in coculture. The downregulated MMP-9 mRNA may be caused by TIMP-1 secretion from BMMSC. Our cell culture system provides a powerful tool for investigating the molecular and cellular changes in microglia-BMMSC cocultures.
Insights
Bone marrow mesenchymal stem cells (BMMSC) can modulate microglia, the brain's immune cells, after central nervous system (CNS) injury. This study shows BMMSC influence microglia activation and inflammatory responses in vitro, offering potential therapeutic insights.
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Microglia activation and inflammation are key responses to central nervous system (CNS) injury.
- Bone marrow mesenchymal stem cells (BMMSC) are investigated for CNS injury treatment due to their anti-inflammatory and paracrine effects.
- The direct impact of BMMSC on microglia in situ remains incompletely understood.
Purpose of the Study:
- To investigate the direct effects of BMMSC on lipopolysaccharide (LPS)-stimulated microglia in vitro.
- To compare the characteristics and modulatory effects of BMMSC cultured in serum-containing and serum-free conditions.
Main Methods:
- In vitro transwell co-culture assay was employed to study microglia-BMMSC interactions.
- BMMSC were cultured under serum (BMMSC) and serum-free (BMMSC-sf) conditions.
- Characterization of BMMSC involved assessing surface markers, morphology, differentiation potential, and secreted factors.
Main Results:
- BMMSC and BMMSC-sf cultures expressed key mesenchymal stem cell markers.
- BMMSC-sf exhibited sphere-like structures with reduced CD29 and CD90 expression compared to fibroblast-like BMMSC.
- BMMSC demonstrated greater differentiation potential into neural-like cells and released significant levels of TIMP-1 and VEGF, potentially downregulating MMP-9 mRNA.
Conclusions:
- BMMSC possess the capacity to modulate microglia activation and inflammatory responses in a co-culture system.
- The study establishes a valuable in vitro model for dissecting molecular and cellular interactions between microglia and BMMSC.
- Findings suggest BMMSC-derived factors like TIMP-1 play a role in regulating microglial inflammatory pathways relevant to CNS injury.
