Cardiopoietic stem cells have reached advanced clinical testing for ischemic heart failure. To profile their molecular influence on recipient hearts, systems proteomics was here applied in a chronic model of infarction randomized with and without human cardiopoietic stem cell treatment. Multidimensional label-free tandem mass spectrometry resolved and quantified 3987 proteins constituting the cardiac proteome. Infarction altered 450 proteins, reduced to 283 by stem cell treatment. Notably, cell therapy non-stochastically reversed a majority of infarction-provoked changes, remediating 85% of disease-affected protein clusters. Pathway and network analysis decoded functional reorganization, distinguished by prioritization of vasculogenesis, cardiac development, organ regeneration, and differentiation. Subproteome restoration nullified adverse ischemic effects, validated by echo-/electro-cardiographic documentation of improved cardiac chamber size, reduced QT prolongation and augmented ejection fraction post-cell therapy. Collectively, cardiopoietic stem cell intervention transitioned infarcted hearts from a cardiomyopathic trajectory towards pre-disease. Systems proteomics thus offers utility to delineate and interpret complex molecular regenerative outcomes.

心脏干细胞已达到针对缺血性心力衰竭的高级临床测试。为了描述它们对受体心脏的分子影响，将系统蛋白质组学应用于有或没有人心脏生成干细胞治疗的随机性梗塞慢性模型中。多维无标记串联质谱法对构成心脏蛋白质组的3987种蛋白质进行了解析和定量。梗死改变了450种蛋白质，通过干细胞治疗减少到283种。值得注意的是，细胞疗法非随机地逆转了大部分由梗死引起的变化，修复了受疾病影响的蛋白质簇的85％。途径和网络分析解码了功能重组，其特征在于血管生成，心脏发育，器官再生和分化的优先次序。蛋白质组学的恢复消除了缺血性不良反应，已通过回声/心电图记录证实了改善的心腔大小，减少的QT延长和增加的细胞治疗后射血分数。总的来说，心肌干细胞干预使梗塞的心脏从心肌病轨迹过渡到疾病前期。因此，系统蛋白质组学可用于描述和解释复杂的分子再生结果。