Iso Yoshitaka, Spees Jeffrey L, Serrano Claudia, Bakondi Benjamin, Pochampally Radhika, Song Yao-Hua, Sobel Burton E, Delafontaine Patrick, Prockop Darwin J
Center for Gene Therapy, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Biochem Biophys Res Commun. 2007 Mar 16;354(3):700-6. doi: 10.1016/j.bbrc.2007.01.045. Epub 2007 Jan 17.
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.
本研究的目的是确定静脉注射来自人骨髓的多能基质细胞（hMSCs）能否在不长期植入的情况下改善心肌梗死后的心脏功能，从而确定短暂的旁分泌效应或分泌因子是否是产生有益作用的原因。将hMSCs全身注射到患有急性心肌梗死的免疫缺陷小鼠体内。与对照组相比，hMSC治疗组心肌梗死后的心脏功能和纤维化得到显著改善。然而，尽管心脏功能有所改善，但心肌梗死后3周心脏中未发现明显的hMSC植入。微阵列分析和酶联免疫吸附测定表明，培养的hMSCs表达并分泌多种保护因子。在模拟组织缺血的条件下，hMSCs分泌的因子可防止培养的心肌细胞和内皮细胞死亡。hMSCs的有益作用似乎反映了分泌因子的影响，而非植入、分化或细胞融合的影响。
