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本帖最后由 hzangs 于 2015-12-14 14:35 编辑
2015年8月11日 J Am Coll Cardiol杂志online一篇研究:
Tseliou, E., et al. (2015). "Fibroblasts Rendered Antifibrotic, Antiapoptotic, and Angiogenic by Priming With Cardiosphere-Derived Extracellular Membrane Vesicles." J Am Coll Cardiol 66(6): 599-611.
BACKGROUND: Cardiosphere-derived cells mediate therapeutic regeneration in patients after myocardial infarction and are undergoing further clinical testing for cardiomyopathy. The beneficial effects of cardiosphere-derived cells are mediated by the secretion of exosomes and possibly other extracellular membrane vesicles (EMVs).
OBJECTIVES: This study sought to investigate the effect of cardiosphere-derived EMVs (CSp-EMVs) on fibroblasts in vitro and tested whether priming with CSp-EMVs could confer salutary properties on fibroblasts in vivo.
METHODS: CSp-EMVs were isolated from serum-free media conditioned for 3 days by cardiospheres. Dermal fibroblasts were primed with CSp-EMVs for 24 h followed by exosomal micro-ribonucleic acid profiling. In vivo, we injected CSp-EMV-primed or -unprimed dermal fibroblasts (or CSp-EMVs) in a chronic rat model of myocardial infarction and defined the functional and structural consequences.
RESULTS: CSp-EMVs amplified their own biological signals: exposure of "inert" fibroblasts to CSp-EMVs rendered the fibroblasts therapeutic. Intramyocardially injected CSp-EMV-primed (but not unprimed) fibroblasts increased global pump function and vessel density while reducing scar mass. CSp-EMV priming caused fibroblasts to secrete much higher levels of stromal-cell-derived factor 1 and vascular endothelial growth factor and dramatically changed the micro-ribonucleic acid profile of fibroblast-secreted EMVs in vitro. The priming was followed by significant angiogenic and cardioprotective effects.
CONCLUSIONS: CSp-EMVs alter fibroblast phenotype and secretome in a salutary positive-feedback loop. The phenotypic conversion of inert cells to therapeutically active cells reveals a novel mechanism for amplification of exosome bioactivity.
大意为,Cardiosphere来源的细胞分泌的exosome处理的fibroblast具有抗纤维化、抗凋亡、促血管新生作用。
Cardiosphere来源的细胞可介导心梗后的心肌再生,并正在心肌症的临床试验。已有研究表明Cardiosphere细胞的这种保护作用是由exosome和其他细胞外膜泡的分泌作用介导的。
这篇工作旨在研究cardiosphere来源的细胞外膜泡 (CSp-EMVs) 在体外成纤维细胞上的作用,检测CSp-EMVs预处理的成纤维细胞是否在体内介导有益的作用。
结果显示CSp-EMVs预处理的成纤维细胞具有治疗作用。心肌内注射CSp-EMVs预处理的成纤维细胞可改善心梗后心功能,促进血管新生、减少疤痕面积。CSp-EMVs预处理使成纤维细胞分泌大量的SDF-1和VEGF,并且显著改变成纤维细胞分泌的细胞外膜泡里的微小RNA的组成。
同期的J Am Coll Cardiol 上出了这篇paper的EDITORIAL COMMENT:
Liang, Y. and S. Sahoo (2015). "Exosomes Explosion for Cardiac Resuscitation." J Am Coll Cardiol 66(6): 612-615.
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