Adipose-Derived Stem Cells Modulate BV2 Microglial M1/M2 Polarization by Producing GDNF

Area of Science:

• Neuroscience
• Immunology
• Regenerative Medicine

Background:

• Neuroinflammation is central to neurological disease pathogenesis, with microglial cells (MG) playing a key role.
• Microglia polarize into M1 (proinflammatory) and M2 (anti-inflammatory/reparative) phenotypes, making polarization a therapeutic target.
• Glial cell-derived neurotrophic factor (GDNF) is a neuroprotective mediator in neurological conditions.

Purpose of the Study:

• To investigate if adipose-derived stem cells (ADSCs) produce GDNF.
• To determine the effects of GDNF on microglial M1/M2 polarization.
• To explore if GDNF modulates microglial activation via the PI3K/AKT pathway.

Main Methods:

• Pretreatment of microglia with ADSCs or GDNF.
• Stimulation of microglia with lipopolysaccharide (LPS) or interleukin-4 (IL-4).
• Assessment of cytokine secretion and microglial phenotype.
• Analysis of the PI3K/AKT signaling pathway.

Main Results:

• ADSCs and GDNF downregulated inflammatory cytokines in LPS-stimulated microglia.
• ADSCs and GDNF upregulated anti-inflammatory mediators in IL-4-stimulated microglia.
• GDNF inhibited the M1 phenotype and promoted the M2 phenotype in microglia, mediated by the PI3K/AKT pathway.

Conclusions:

• GDNF secreted by ADSCs effectively modulates microglial polarization.
• GDNF shifts microglia from a proinflammatory M1 to an anti-inflammatory M2 phenotype.
• ADSC-derived GDNF holds promise for regulating neuroinflammatory disorders via the PI3K/AKT pathway.