Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.
Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.
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作者：
间充质干细胞已成为一系列神经损伤的潜在治疗方法。多发性硬化症是一种以少突胶质细胞和髓磷脂为靶点的自身免疫性疾病，在多发性硬化症动物模型中，用人间充质干细胞治疗可导致功能改善，这反映了免疫反应和髓磷脂修复的调节。本研究表明，来自人间充质干细胞的条件培养基（CM）可减少mog35 - 55诱导的小鼠EAE的功能缺陷，并促进少突胶质细胞和神经元的发育。功能分析确定了肝细胞生长因子（HGF）及其主要受体cMet在MSCs刺激的EAE恢复、神经细胞发育和髓鞘再生中的关键作用。活性的MSC-CM含有HGF，外源性提供的HGF促进EAE的恢复，而cMet和抗HGF抗体阻断HGF和MSC-CM介导的功能恢复。在溶卵磷脂诱导的大鼠脊髓背病变和切片培养中，用HGF进行全身治疗可显著加速髓鞘再生。总之，这些数据强烈暗示HGF在多发性硬化症动物模型中介导msc刺激的功能恢复。
Mesenchymal stem cells have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium (CM) from human MSCs reduces functional deficits in mouse MOG35–55-induced EAE and promotes the development of oligodendrocytes and neurons. Functional assays identify a critical role for Hepatocyte Growth Factor (HGF) and its primary receptor cMet in MSCs stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contains HGF and exogenously supplied HGF promotes recovery in EAE while cMet and anti-HGF antibodies block the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF dramatically accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.
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DOI：
10.1016/s0165-3806(97)00108-9
发表时间：
1997-09-20
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Achim, CL;Katyal, S;Michalopoulos, GK
通讯作者：
Michalopoulos, GK
DOI：
10.1196/annals.1444.014
发表时间：
2008-01-01
期刊：
YEAR IN NEUROLOGY 2008
影响因子：
--
作者：
Ben-Hur, Tamir;Goldman, Steven A.
通讯作者：
Goldman, Steven A.
影响因子：
6.2
作者：
Ghasemlou, Nader;Jeong, Suh Young;David, Samuel
通讯作者：
David, Samuel
影响因子：
15.9
作者：
Kuroiwa, T;Kakishita, E;Iwasaki, T
通讯作者：
Iwasaki, T
影响因子：
4.8
作者：
Koç, ON;Day, J;Krivit, W
通讯作者：
Krivit, W