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Cardioprotective effect of the secretome of Sca-1+ and Sca-1- cells in heart failure: not equal, but equally important?
Cardiovascular Research ( IF 10.2 ) Pub Date : 2020-03-01 , DOI: 10.1093/cvr/cvz140
Stephanie Könemann 1, 2 , Luiz V Sartori 1 , Stefan Gross 1, 2 , Stefan Hadlich 3 , Jens-Peter Kühn 3 , Rasmita Samal 1, 2 , Martin Bahls 1, 2 , Stephan B Felix 1, 2 , Kristin Wenzel 1, 2
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AIMS Both progenitor and differentiated cells were previously shown to secrete cardioprotective substances, but so far there has been no direct comparison of the paracrine effects of the two cell types on heart failure. The study sought to compare the paracrine effect of selected progenitors and the corresponding non-progenitor mononuclear cardiac cells on the cardiac function of transgenic heart failure mice. In addition, we aimed to further enhance the paracrine effect of the cells via pretreatment with the heart failure mediator aldosterone. METHODS AND RESULTS Transgenic heart failure mice were injected with the supernatant of murine cardiac stem cell antigen-1 positive (Sca-1+) and negative (Sca-1-) cells with or without aldosterone pretreatment. Cardiac function was determined using small animal magnetic resonance imaging. In addition, heart failure markers were determined using enzyme-linked immunosorbent assay, RT-PCR, and bead-based multiplexing assay. While only the secretome of aldosterone pretreated Sca-1+ cells led to a significant improvement in cardiac function, N-terminal pro brain natriuretic peptide plasma levels were significantly lower and galectin-1 levels significantly higher in mice that were treated with either kind of secretome compared with untreated controls. CONCLUSION In this first direct comparison of the paracrine effects of progenitor cells and a heterogeneous population of mononuclear cardiac cells the supernatants of both cell types showed cardioprotective properties which might be of great relevance for endogenous repair. During heart failure raised aldosterone levels might further increase the paracrine effect of progenitor cells.

中文翻译:

Sca-1 +和Sca-1-细胞的分泌基因组对心力衰竭的心脏保护作用:不相等,但同样重要吗?

目的以前曾证明祖细胞和分化细胞均会分泌心脏保护性物质,但到目前为止,尚无直接比较两种细胞对心力衰竭的旁分泌作用的信息。该研究试图比较所选祖细胞和相应的非祖单个核心脏细胞对转基因心力衰竭小鼠心脏功能的旁分泌作用。此外,我们旨在通过心力衰竭介导的醛固酮预处理进一步增强细胞的旁分泌作用。方法和结果转基因心力衰竭小鼠被注射鼠心脏干细胞抗原-1阳性(Sca-1 +)和阴性(Sca-1-)细胞的上清液,并进行或不进行醛固酮预处理。使用小动物磁共振成像确定心脏功能。此外,使用酶联免疫吸附测定,RT-PCR和基于磁珠的多重测定确定心力衰竭标记。尽管仅醛固酮预处理的Sca-1 +细胞的分泌组可显着改善心脏功能,但用两种分泌组治疗的小鼠的N端前脑利钠肽血浆水平均显着降低,而半乳糖凝集素1水平显着升高。与未处理的对照组相比。结论在对祖细胞和异种单核心肌细胞群体的旁分泌作用进行的首次直接比较中,两种细胞类型的上清液均显示出心脏保护特性,这可能与内源性修复有很大关系。心力衰竭期间,醛固酮水平升高可能进一步增加祖细胞的旁分泌作用。
更新日期:2020-02-20
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