Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.
Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.
复制标题
静脉注射HMSC改善了小鼠的心肌梗塞，因为栓塞在肺中的细胞被激活以分泌抗炎蛋白TSG-6。
DOI：
10.1016/j.stem.2009.05.003
复制
发表时间：
2009-07-02
期刊：
影响因子：
23.9
通讯作者：
Prockop DJ
中科院分区：
文献类型：
--
作者：
Lee RH;Pulin AA;Seo MJ;Kota DJ;Ylostalo J;Larson BL;Semprun-Prieto L;Delafontaine P;Prockop DJ
人DNA和mRNA的定量分析用于检验静脉注射人多能基质细胞（hMSCs）可以在没有明显植入的情况下增强组织修复的悖论。小鼠静脉注射2 × 106个hMSCs后，大部分细胞以栓塞形式滞留在肺内。肺内细胞消失，半衰期约为24小时，其余6个组织均出现<1000个细胞。肺组织中hMSCs上调多个基因表达，抗炎蛋白TSG-6显著升高。心肌梗死后，静脉注射hMSCs，而不是用TSG-6 siRNA转导的hMSCs，炎症反应降低，梗死面积减小，心功能改善。静脉注射重组TSG-6也能减少炎症反应，缩小梗死面积。结果表明，静脉输注MSCs后动物模型和患者的改善至少部分可以通过激活MSCs分泌TSG-6来解释。
Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 × 106 hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. I.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.
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DOI：
10.1165/rcmb.2006-0018oc
发表时间：
2007-01-01
影响因子：
6.4
作者：
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影响因子：
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