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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Mesenchymal stem cells enhance microglia M2 polarization and attenuate neuroinflammation through TSG-6
Yi Liu1, Rong Zeng2, Yezhong Wang3
1Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China; Department of Neurosurgery and Neurosurgical Disease Research Centre, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Abstract:
Microglia are the primary cells that exert immune function in the central nervous system (CNS), and they play an important role in the pathogenesis and progression of neuroinflammation-related diseases. Mesenchymal stem cells (MSCs) have been demonstrated to promote functional recovery in many neurological diseases. The mechanisms underlying this may be that MSCs can reduce inflammatory responses through various soluble factors. Among these factors, tumor necrosis factor-α-induced gene/protein 6 (TSG-6) is a key factor influencing MSCs immunomodulatory properties; however, the precise mechanisms underlying the anti-inflammatory effects are not fully understood. Here, we aim to investigate the potential effects of MSCs on neuroinflammation and to reveal the underlying mechanisms. First, we confirmed that administration of MSCs could inhibit the lipopolysaccharide (LPS)-induced neuroinflammatory responses in a mouse model. Then, we found that MSCs promoted M2 polarization and inhibited M1 polarization both in vivo and in vitro. Moreover, we demonstrated that the effect of MSCs on microglial polarization was dependent on TSG-6. This study demonstrated that MSCs promoted M2 polarization of microglia via TSG-6, thus conferring anti-neuroinflammatory effects.
Insights
Mesenchymal stem cells (MSCs) reduce neuroinflammation by promoting M2 microglial polarization. This effect is mediated by tumor necrosis factor-α-induced gene/protein 6 (TSG-6), offering a potential therapeutic strategy for neurological diseases.
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Microglia are key immune cells in the central nervous system (CNS), crucial in neuroinflammation.
- Mesenchymal stem cells (MSCs) show therapeutic potential in neurological diseases, likely via immunomodulation.
- Tumor necrosis factor-α-induced gene/protein 6 (TSG-6) is implicated in MSCs' anti-inflammatory actions, but mechanisms require clarification.
Purpose of the Study:
- To investigate the effects of MSCs on neuroinflammation.
- To elucidate the underlying mechanisms of MSC-mediated anti-neuroinflammatory effects.
- To determine the role of TSG-6 in MSC-induced microglial modulation.
Main Methods:
- Utilized a lipopolysaccharide (LPS)-induced mouse model of neuroinflammation.
- Administered MSCs and assessed their impact on microglial polarization in vivo and in vitro.
- Investigated the dependency of MSC effects on TSG-6.
Main Results:
- MSCs administration inhibited LPS-induced neuroinflammatory responses.
- MSCs promoted M2 microglial polarization and inhibited M1 polarization.
- The immunomodulatory effects of MSCs on microglia were dependent on TSG-6.
Conclusions:
- MSCs exert anti-neuroinflammatory effects by promoting microglial M2 polarization.
- TSG-6 is a critical mediator of MSC-induced M2 polarization.
- Targeting MSCs and TSG-6 presents a promising therapeutic avenue for neuroinflammatory conditions.
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