title: Bone marrow-derived mesenchymal stem cells maintain the resting phenotype of microglia and inhibit microglial activation.
abstract: Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown in many animal models to have a therapeutic effect on neural damage. Such a therapeutic effect is attributed to the fact that BMSCs have the ability to differentiate into neurons and to produce trophic factors, but there is little information available in the literature concerning whether BMSCs play a therapeutic role by affecting microglial activity. In this study, we triggered an inflammatory response situation in vitro by stimulating microglia with the bacterial endotoxin lipopolysaccharide (LPS), and then culturing these microglia with BMSC-conditioned medium (BMSC-CM). We found that BMSC-CM significantly inhibited proliferation and secretion of pro-inflammatory factors by activated microglia. Furthermore, we found that the phagocytic capacity of microglia was also inhibited by BMSC-CM. Finally, we investigated whether the induction of apoptosis and the production of nitric oxide (NO) were involved in the inhibition of microglial activation. We found that BMSC-CM significantly induced apoptosis of microglia, while no apoptosis was apparent in the LPS-stimulated microglia. Our study also provides evidence that NO participates in the inhibitory effect of BMSCs. Our experimental results provide evidence that BMSCs have the ability to maintain the resting phenotype of microglia or to control microglial activation through their production of several factors, indicating that BMSCs could be a promising therapeutic tool for treatment of diseases associated with microglial activation.
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yan
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Chengmei
authors.initials: C
authors.lastname: Sun
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China ; Department of Neurosurgery, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China ; Department of Neurosurgery, Guangzhou First People's Hospital, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China ; Department of Neurology, The First People's Hospital of Foshan, Foshan, China.
authors.forename: Lingmei
authors.initials: L
authors.lastname: Peng
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Sun
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China ; Department of Neurosurgery, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Qin
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China ; Department of Neurosurgery, Guangzhou First People's Hospital, Guangzhou, China.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Chen
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Huang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Bingke
authors.initials: B
authors.lastname: Lv
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Mouxuan
authors.initials: M
authors.lastname: Du
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zou
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Cai
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lingsha
authors.initials: L
authors.lastname: Qin
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000254:growth & development* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide