Related Experiment Video
Updated: Apr 27, 2026
Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility
Published on: April 13, 2017
Mesenchymal stem cells induce the ramification of microglia via the small RhoGTPases Cdc42 and Rac1
Veronika E Neubrand1, Marta Pedreño, Marta Caro
1Institute of Parasitology and Biomedicine López-Neyra, Dept. Cell Biology and Immunology, IPBLN-CSIC, Avda. Conocimiento, PT Ciencias de La Salud, Granada, Spain.
Abstract:
Activated microglia play a central role in the course of neurodegenerative diseases as they secrete cytotoxic substances which lead to neuronal cell death. Understanding the mechanisms that drive activation of microglia is essential to reverse this phenotype and to protect from neurodegeneration. With some exceptions, evidence indicates that changes in cell morphology from a star shape to a round and flat shape accompany the process of activation in microglia. In this study, we investigated the effect of adipose-tissue-derived mesenchymal stem cells (ASCs), which exert important anti-inflammatory actions, in microglia morphology. Microglia exposed to ASCs or their secreted factors (conditioned medium) underwent a cell shape change into a ramifying morphology in basal and inflammatory conditions, similar to that observed in microglia found in healthy brain. Colony-stimulating factor-1 secreted by ASCs played a critical role in the induction of this phenotype. Importantly, ASCs reversed the activated round phenotype induced in microglia by bacterial endotoxins. The ramifying morphology of microglia induced by ASCs was associated with a decrease of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6, an increase in phagocytic activity, and the upregulation of neurotrophic factors and of Arginase-1, a marker for M2-like regulatory microglia. In addition, activation of the phosphoinositide-3-kinase/Akt pathway and the RhoGTPases Rac1 and Cdc42 played a major role in the acquisition of this phenotype. Therefore, these RhoGTPases emerge as key players in the ramification of microglia by anti-inflammatory agents like ASCs, being fundamental to maintain the tissue-surveying, central nervous system supporting state of microglia in healthy conditions.
Insights
Adipose-derived stem cells (ASCs) promote a healthy microglia morphology, reversing detrimental activation. This shift involves key signaling pathways and reduces neuroinflammation, offering potential for neurodegenerative disease treatment.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Activated microglia contribute to neurodegeneration by releasing cytotoxic factors.
- Microglial activation is characterized by a change from ramified to round morphology.
- Understanding microglia activation is crucial for developing neuroprotective strategies.
Purpose of the Study:
- To investigate the effect of adipose-tissue-derived mesenchymal stem cells (ASCs) on microglia morphology.
- To elucidate the mechanisms by which ASCs modulate microglial phenotype.
- To assess the therapeutic potential of ASCs in reversing microglial activation.
Main Methods:
- Exposure of microglia to ASCs and their conditioned medium.
- Analysis of microglial cell morphology.
- Measurement of cytokine levels (TNF-α, IL-6), phagocytic activity, and neurotrophic factor expression.
- Investigation of signaling pathways including phosphoinositide-3-kinase/Akt and RhoGTPases (Rac1, Cdc42).
Main Results:
- ASCs induced a ramifying microglia morphology, mimicking a healthy state, under basal and inflammatory conditions.
- Colony-stimulating factor-1 secreted by ASCs was critical for this morphological change.
- ASCs reversed the activated, round microglia phenotype induced by bacterial endotoxins.
- The ramified morphology correlated with reduced pro-inflammatory cytokines, increased phagocytosis, and elevated neurotrophic factors and Arginase-1.
- Activation of the PI3K/Akt pathway and RhoGTPases Rac1/Cdc42 was essential for ASC-induced microglial ramification.
Conclusions:
- ASCs effectively restore a healthy, ramified microglia morphology and function.
- Colony-stimulating factor-1 and RhoGTPases are key mediators of ASC-induced microglial modulation.
- ASCs demonstrate significant anti-inflammatory and neuroprotective potential by regulating microglial phenotype.
- Targeting RhoGTPases may be a viable strategy for leveraging ASCs in treating neurodegenerative diseases.
More Related Videos
Related Concept Videos
01:21Cell Polarization by Rho Proteins
01:19Mesenchymal Stem Cells