Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome
Open Access
- 12 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in npj Regenerative Medicine
- Vol. 5 (1), 5
- https://doi.org/10.1038/s41536-020-0091-6
Abstract
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.Keywords
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