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.

心脏生成干细胞已达到治疗缺血性心力衰竭的高级临床测试。为了分析它们对受体心脏的分子影响，系统蛋白质组学被应用于慢性梗塞模型，随机使用和不使用人类心脏生成干细胞治疗。多维无标记串联质谱法解析并定量了构成心脏蛋白质组的 3987 个蛋白质。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，细胞疗法非随机逆转了大多数梗塞引发的变化，修复了 85% 受疾病影响的蛋白质簇。通路和网络分析解码了功能重组，其特点是血管生成、心脏发育、器官再生和分化的优先顺序。亚蛋白质组恢复消除了不利的缺血效应，通过回波/心电图记录证实细胞治疗后心室大小改善、QT 延长减少和射血分数增加。总的来说，心肌干细胞干预将梗塞心脏从心肌病轨迹转变为疾病前状态。因此，系统蛋白质组学为描述和解释复杂的分子再生结果提供了实用性。