4.6 Article

Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome

Journal

STEM CELLS TRANSLATIONAL MEDICINE
Volume 10, Issue 9, Pages 1320-1328

Publisher

OXFORD UNIV PRESS
DOI: 10.1002/sctm.20-0509

Keywords

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

Funding

  1. Medical Scientist Training Program at Mayo Clinic
  2. Mayo Clinic Center for Regenerative Medicine
  3. Michael S. and Mary Sue Shannon Family
  4. Van Cleve Cardiac Regenerative Medicine Program
  5. Marriott Family Foundation
  6. National Institutes of Health [T32 GM 65841, R01 HL134664]

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Stem cell paracrine activity, specifically secreted proteins by cardiopoietic cells, play a key role in cardiac repair. Through systems analytics and RNA sequencing, miR-146 was identified as a regulator upstream of the decoded secretome. The therapeutic impact of cardiopoietic cell therapy on infarcted hearts is influenced by the inherent vasculogenic properties and smooth muscle differentiation of the secreted proteins.
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.

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