Chinese Journal of Tissue Engineering Research

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Microglia activation stimulates bone marrow mesenchymal stem cells to release gliocyte-derived neurotrophic factor for protection of dopaminergic neurons

Fan Dong-yan1, Wang Ping2, Liu Ran1, 3, Niu Feng-lan1, Du Bo2   

  1. 1Teaching and Research Section of Toxicology, College of Public Health, Jilin University, Changchun   130021, Jilin Province, China;
    2Department of Otolaryngology, Head and Neck Surgery, First Clinical Hospital, Jilin University, Changchun   130021, Jilin Province, China;
    3Changchun Blood Center, Changchun   130000, Jilin Province, China
  • Online:2010-02-05 Published:2010-02-05
  • Contact: Du Bo, Doctor, Associate professor, Department of Otolaryngology, Head and Neck Surgery, First Clinical Hospital, Jilin University, Changchun 130021, Jilin Province, China dubo2222@hotmail.com
  • About author:Fan Dong-yan, Studying for doctorate, Teaching and Research Section of Toxicology, College of Public Health, Jilin University, Changchun 130021, Jilin Province, China Dongyan_fan@yahoo.com.cn

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Abstract:

BACKGROUND: Studies are very few regarding the specific reaction of bone marrow mesenchymal stem cells (BMSCs) to activated microglia. Moreover, it remains unclear how MSCs maintain dopaminergic neuronal survival under specific microenvironment.

OBJECTIVE: To explore the effect of BMSCs stimulated by activated microglia on dopaminergic neuron survival.

METHODS: BMSCs were isolated from Wistar rats by attachment method, and in vitro cultured; microglia was activated, and dopaminergic neurons were cultured by enzyme digestion method. The experiment included 5 groups: BMSCs, microglia, lipopolysaccharide (LPS)+microglia; BMSCs+LPS+microglia groups, in which the dopaminergic neurons were cultured with corresponding culture medium; the dopaminergic neurons alone group was cultured with 10% fetal bovine serum+ DMEM/F12. The effect of different microenvironment on dopaminergic neuron survival and gliocyte-derived neurotrophic factor released from BMSCs were detected by immunofluorescence technique.

RESULTS AND CONCLUSION: The release of gliocyte-derived neurotrophic factor in groups involving BMSCs was greater than corresponding control group. Tyrosine hydroxylase immunofluorescence showed that neuronal survival of dopaminergic neurons alone group was 15%, microglia group was 10%, LPS+microglia was 5%, but BMSCs+LPS+microglia group was 28%, significantly greater than the other groups (P < 0.05). In addition, survival of in vitro cultured dopaminergic neurons was decreased with increasing culture duration, but the survival of dopaminergic neurons in group involving BMSCs was significantly greater than corresponding control group. This indicates that microglia activation stimulated BMSCs to upregulate gliocyte-derived neurotrophic factor to prevent dopaminergic neurons from toxic injury, and inhibit delayed death of dopaminergic neurons.

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