我们对msc的干细胞特性关注了太多而忽视了它的另外一个重要特性——组织损伤修复事件中扮演着特殊的角色,修复?促炎?护瘤?
Neuroprotective effects of human mesenchymal stem cells on dopaminergic neurons through anti-inflammatory action
You-Joung Kim 1, Hyun-Jung Park 1, Gwang Lee 1, Oh Young Bang 2, Young Hwan Ahn 1, Eunhye Joe 3, Hyun Ok Kim 4, Phil Hyu Lee 5 *
Glia, Published Online: 25 Jul 2008
email: Phil Hyu Lee (
phisland@chol.com)
Funded by:
Ministry of Science and Technology, Republic of Korea [Stem Cell Research Center of the 21st Century Frontier Research Program (SC-4111)]
Keywords
mesenchymal stem cells • neuroprotective effect • anti-inflammatory • Parkinson's disease
Abstract
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 an important role in the pathogenesis of PD. In this study, we used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether human mesenchymal stem cells (hMSCs) have a protective effect on the dopaminergic system through anti-inflammatory mechanisms. The hMSC treatment significantly decreased LPS-induced microglial activation, tumor necrosis factor (TNF)-, inducible nitric oxide synthase (iNOS) mRNA expression, and production of NO and TNF- compared with the LPS-only treatment group. In co-cultures of microglia and mesencephalic dopaminergic neurons, hMSC treatment significantly decreased the loss of tyrosine hydroxylase-immunopositive (TH-ip) cells. The hMSC treatment in rats showed that TH-ip neuronal loss induced by LPS stimulation in the SN was considerably decreased and was clearly accompanied by a decrease in activation of microglia, as well as TNF- and iNOS mRNA expression and production of TNF-. These data suggest that hMSCs have a neuroprotective effect on dopaminergic neurons through anti-inflammatory actions mediated by the modulation of microglial activation. Along with various trophic effects and trans-differentiational potency, the anti-inflammatory properties of MSCs could have major therapeutic implications in the treatment of PD.