Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment
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DOI:
10.1016/j.bbrc.2007.01.045
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发表时间:
2007-03-16
影响因子:
3.1
通讯作者:
Prockop, Darwin J.
Prockop, Darwin J.
中科院分区:
生物学4区
文献类型:
--
作者:
Iso, Yoshitaka;Spees, Jeffrey L.;Prockop, Darwin J.

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本研究的目的是确定静脉内给予人骨髓多能基质细胞(hMSCs)是否可以改善心肌梗死(MI)后的心脏功能,而无需长期植入,因此是否短暂的旁分泌效应或分泌因子负责所赋予的好处。将hMSC全身注射到患有急性MI的免疫缺陷小鼠中。与对照组相比,hMSC治疗组心肌梗死后的心功能和纤维化明显改善。然而,尽管心脏改善,但MI后3周心脏中没有明显的hMSC植入。微阵列分析和ELISA表明,多种保护因子表达和分泌的hMSCs在培养。在模拟组织缺血的条件下,hMSCs分泌的因子阻止了培养的心肌细胞和内皮细胞的细胞死亡。hMSC的有利作用似乎反映了分泌因子的影响,而不是移植、分化或细胞融合。(c)2007爱思唯尔公司All rights reserved.
The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion. (c) 2007 Elsevier Inc. All rights reserved.