期刊
MOLECULAR NEUROBIOLOGY
卷 55, 期 6, 页码 4763-4776出版社
SPRINGER
DOI: 10.1007/s12035-017-0681-5
关键词
Prostaglandin; Parkinson's disease; Dopaminergic neurons; Mesenchymal stromal cells; Neuroprotection
资金
- Spanish Ministry of Economy and Competitiveness [BFU2015-70523]
- Spanish Ministry of Health [RD12/0019/0020, RD16/0011/0016]
- Spanish Ministry of Health (CIBERNED)
- Galician Government (XUGA)
- Galician Government (Centro singular de investigacion de Galicia acreditacion) [ED431G/05]
- European Regional Development Fund (ERDF)
Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson's disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having both neuroprotective and neurorescue activities against effects of dopaminergic neurotoxin 6-hydroxydopamine. We found that lipid removal, inhibition of the prostaglandin E2 receptor 2 (EP2), and its signaling pathway were able to block the effects of MSC-CM on a pure population of dopaminergic neurons. Moreover, in primary mesencephalic cultures and hiPSC-derived neurons, inhibition of EP2 signaling caused a reduction in the number of dopaminergic neurons obtained in culture. Taken together, our results demonstrate for the first time the involvement of prostaglandin signaling from MSC in dopaminergic neuron survival through EP2 receptors, and suggest new approaches for treatment of Parkinson's disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据