Neuroprotective Effect of Human Mesenchymal Stem Cell on Dopaminergic Neurons by Anti-inflammatory Action

Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays a critical role in the pathogenesis of PD. The present study was to evaluate effect of human bone marrow-derived mesenchymal stem cell (hMSCs) on modulation of neuroinflammation. We used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether hMSCs have a protective effect on the dopaminergic system through anti-inflammatory mechanism. hMSCs treatment significantly decreased LPS-induced microglial activation and production of pro-inflammatory cytokines compared to LPS-only treatment group. In co-culture cells of microglia and mesencephalic dopaminergic neurons, hMSCs treatment resulted in a significant reduction of dopaminergic neuronal loss induced by LPS stimulation. In animal study, hMSCs treatment significantly increased survival of TH-ip cells at 7 and 14 days following hMSCS injection, approximately two times more than the LPS-only treatment, which was clearly accompanied by a decrease in activation of microglia. Additionally, cytokine assay in the SN showed that hMSCs treatment significantly down regulated the LPS-induced increase in the expression of TNF-α and iNOS mRNA following LPS stimulation. TNF-α and iNOS release were also significantly decreased in the hMSCs group when compared to the LPS-only treatment group at 4 hr and 3 day following hMSCS injection. The present study demonstrated that MSCs have a neuroprotective effect on dopaminergic neurons via an anti-inflammatory mechanism mediated by the modulation of microglial activation. Along with various trophic effect and transdifferentiational potency, anti-inflammatory mechanism of MSCs could have major therapeutic implication in the treatment of PD.

Author dc:creator

• 김, 유정

Contributors dc:contributor

• 이, 필휴
• 대학원 의학과
• 200624165

• Human mesenchymal stem cell
• anti-inflammation
• dopaminergic neurons
• mMicroglia
• Parkinson’s disease
• 성체 중간엽 줄기세포
• 항염증
• 도파민 신경세포
• 미세아교세포
• 파킨슨씨병

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005879
000000005879

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1382