Stem cell factor induces polarization of microglia to the neuroprotective phenotype in vitro
Tomoya Terashima1, Yuki Nakae1, Miwako Katagi1
1Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga, Japan.
Abstract:
Microglia are classified mainly into the M1 or M2 phenotypes, which evoke either proinflammatory or neuroprotective responses. Given the association of microglia with the pathogenesis of neuronal diseases, they are in focus as therapeutic targets for the treatment of such conditions. Stem cell factor (SCF) is a ligand for the c-kit receptor, one of the differentiation factors for bone marrow cells. In this study, characteristics of SCF-activated microglia and their effects on neurons were analyzed to investigate the therapeutic potential of SCF in neuronal diseases. SCF was found to induce proliferation, migration, and phagocytosis of microglia. In addition, SCF-derived microglia showed a neuroprotective phenotype expressing anti-inflammatory cytokines, growth factors, and M2 markers as compared to the phenotype shown by granulocyte macrophage-colony stimulating factor-derived microglia expressing inflammatory cytokines and M1 markers. Furthermore, supernatant medium from SCF-activated microglia enhanced cell proliferation and protection from cell death in NSC-34 neuronal cells. We conclude that SCF modulates microglial functions and induces activation of the neuroprotective effects of microglia, which could be used for treatment of neuronal diseases.
Insights
Stem cell factor (SCF) activates microglia, promoting their neuroprotective functions. This suggests SCF as a potential therapeutic agent for treating neuronal diseases by enhancing microglial anti-inflammatory and regenerative capabilities.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the immune cells of the central nervous system, exist in M1 (proinflammatory) and M2 (neuroprotective) phenotypes.
- Dysfunctional microglia are implicated in the pathogenesis of various neuronal diseases, making them attractive therapeutic targets.
Purpose of the Study:
- To investigate the therapeutic potential of Stem Cell Factor (SCF) in neuronal diseases by analyzing SCF-activated microglia.
- To characterize the functional and phenotypic changes in microglia upon SCF stimulation.
Main Methods:
- Microglia were treated with Stem Cell Factor (SCF).
- Microglial proliferation, migration, and phagocytosis were assessed.
- Phenotypic markers (M1/M2) and cytokine expression were analyzed.
- The effects of SCF-activated microglia supernatant on neuronal cells (NSC-34) were evaluated.
Main Results:
- SCF treatment induced microglial proliferation, migration, and phagocytosis.
- SCF-activated microglia exhibited a neuroprotective M2 phenotype, expressing anti-inflammatory cytokines and growth factors.
- Compared to granulocyte-macrophage colony-stimulating factor (GM-CSF)-activated microglia (M1 phenotype), SCF-activated microglia demonstrated a distinct anti-inflammatory profile.
- Supernatant from SCF-activated microglia enhanced neuronal cell proliferation and protected against cell death.
Conclusions:
- Stem cell factor (SCF) effectively modulates microglial functions, shifting them towards a neuroprotective phenotype.
- SCF-activated microglia exhibit enhanced anti-inflammatory and neurotrophic properties.
- SCF holds promise as a therapeutic strategy for neurodegenerative diseases by leveraging the neuroprotective potential of microglia.
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