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对人心肌祖细胞旁分泌机制的新认识。

New insights into paracrine mechanisms of human cardiac progenitor cells.

机构信息

Department of Anaesthesiology, University Hospital Giessen and Marburg, Campus Giessen, Rudolf-Buchheim-Str 7, 35392 Giessen, Germany.

出版信息

Eur J Heart Fail. 2010 Jul;12(7):730-7. doi: 10.1093/eurjhf/hfq063. Epub 2010 Apr 20.

DOI:10.1093/eurjhf/hfq063
PMID:20406797
Abstract

AIMS

Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration in vivo. Understanding the function of CPCs is essential for further implementation of these cells in the treatment of cardiac diseases. The present study tested the hypothesis that adult CPC exert paracrine effects that lead to an improvement in the functional characteristics of cardiomyocytes. This study also investigated whether aging (we included patients aged between 4 months and 81 years) has any effect on the paracrine mechanisms of CPC.

METHODS AND RESULTS

The supernatant of CPC generated both from human and rat hearts-so called 'conditioned cardiosphere medium' improved the contractile behaviour of isolated adult cardiomyocytes in a concentration-dependent manner after incubation for 24 h and increased the SERCA/NCX ratio. The observed positive effects on contractile behaviour were independent of the CPC donors' age. Conditioned cardiosphere media also normalized angiotensin II-induced contractile dysfunction. Cytokines released by CPC into the media were detected by cytokine arrays.

CONCLUSION

The observed diversity of cytokines released by CPC needs to be further elucidated in detail. Nevertheless, CPC are a promising therapeutic approach in the field of cardiac disease. The methods described allow investigation of the underlying paracrine mechanisms in a standardized in vitro situation.

摘要

目的

心脏祖细胞 (CPCs) 已被证明可在体内促进心脏再生。了解 CPC 的功能对于进一步将这些细胞应用于心脏疾病的治疗至关重要。本研究检验了以下假设,即成年 CPC 发挥旁分泌作用,从而改善心肌细胞的功能特性。本研究还调查了年龄(我们纳入了年龄在 4 个月至 81 岁之间的患者)是否对 CPC 的旁分泌机制有任何影响。

方法和结果

来自人心和鼠心的 CPC 的上清液——所谓的“条件心脏球体培养基”,在孵育 24 小时后以浓度依赖性方式改善了分离的成年心肌细胞的收缩行为,并增加了 SERCA/NCX 比值。观察到的对收缩行为的积极影响与 CPC 供体的年龄无关。条件心脏球体培养基还可使血管紧张素 II 诱导的收缩功能障碍正常化。通过细胞因子阵列检测到 CPC 释放到培养基中的细胞因子。

结论

需要进一步详细阐明 CPC 释放的细胞因子的多样性。尽管如此,CPC 仍是心脏疾病治疗领域有前途的治疗方法。所描述的方法允许在标准化的体外情况下研究潜在的旁分泌机制。

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