Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome

D. Kent Arrell, Ruben J. Crespo-Diaz, Satsuki Yamada, Ryounghoon Jeon, Armin Garmany, Sungjo Park, Jeffrey P. Adolf, Christopher Livia, Matthew L. Hillestad, Jozef Bartunek, Atta Behfar, Andre Terzic

Research output: Contribution to journalArticlepeer-review

Abstract

Stem cell paracrine activity is implicated in cardiac repair. Linkage between secretome functionality and therapeutic outcome was here interrogated by systems analytics of biobanked human cardiopoietic cells, a regenerative biologic in advanced clinical trials. Protein chip array identified 155 proteins differentially secreted by cardiopoietic cells with clinical benefit, expanded into a 520 node network, collectively revealing inherent vasculogenic properties along with cardiac and smooth muscle differentiation and development. Next generation RNA sequencing, refined by pathway analysis, pinpointed miR-146 dependent regulation upstream of the decoded secretome. Intracellular and extracellular integration unmasked commonality across cardio-vasculogenic processes. Mirroring the secretome pattern, infarcted hearts benefiting from cardiopoietic cell therapy restored the disease proteome engaging cardiovascular system functions. The cardiopoietic cell secretome thus confers a therapeutic molecular imprint on recipient hearts, with response informed by predictive systems profiling.

Original languageEnglish (US)
JournalStem Cells Translational Medicine
DOIs
StateAccepted/In press - 2021

Keywords

  • cardiopoiesis
  • clinomics
  • heart failure
  • regenerative medicine
  • stem cells
  • systems biology
  • therapy

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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