Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome

D. Kent Arrell, Christian S. Rosenow, Satsuki Yamada, Atta Behfar, Andre Terzic

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Article number5
Journalnpj Regenerative Medicine
Volume5
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Developmental Biology
  • Medicine (miscellaneous)

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