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

• Published in: Stem cells and development Vol. 29; no. 11; p. 714
• Main Authors: Zhong, Zhenzhong, Chen, Ao, Fa, Zhiqiang, Ding, Zhiquan, Xie, Jiayu, Sun, Yujia, Zhang, Run, Wang, Qinghua
• Format: Journal Article
• Language: English
• Published: United States 01.06.2020
• Subjects: Adipose Tissue - cytology; Animals; Cell Differentiation; Cell Line; Cells, Cultured; Coculture Techniques - methods; Culture Media, Conditioned - pharmacology; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Interleukin-4 - genetics; Interleukin-4 - metabolism; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; microglial polarization; PI3K/AKT signaling pathway; neuroinflammation; adipose-derived stem cell; glial cell-derived neurotrophic factor
• ISSN: 1557-8534
• DOI: 10.1089/scd.2019.0235

Neuroinflammation is associated with the pathogenesis of all types of neurological disease, in which microglial cells play a critical role. In response to disturbances in the microenvironment, microglia (MG) become activated and differentiate into either an M1 phenotype, which has a proinflammatory damaging effect, or an M2 phenotype, which plays an anti-inflammatory and reparative role. Thus, modulating microglial polarization is a suitable strategy to treat neuroinflammatory disorders. Glial cell-derived neurotrophic factor (GDNF) is a neurotrophic mediator that exerts neuroprotective effects during neurological diseases. In this study, we predicted that adipose-derived stem cells (ADSCs) could produce GDNF and investigated the effects of GDNF on microglial M1/M2 polarization. Furthermore, we determined whether GDNF modulates microglial activation and polarization via the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway. We found that the secretion of inflammatory cytokines in lipopolysaccharide-stimulated MG was downregulated, whereas the anti-inflammatory mediators in interleukin-4-stimulated MG were upregulated obviously, following pretreatment with ADSCs or GDNF. In addition, GDNF produced by ADSCs inhibited the MG M1 phenotype and promoted the M2 phenotype by upregulating the PI3K/ATK pathway. These results reveal that GDNF produced by ADSCs might be useful for the regulation of neuroinflammatory disorders.