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.

Details

Title
Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome
Author
Arrell, D Kent 1   VIAFID ORCID Logo  ; Ruben J. Crespo‐Diaz 2 ; Yamada, Satsuki 3   VIAFID ORCID Logo  ; Jeon, Ryounghoon 4   VIAFID ORCID Logo  ; Garmany, Armin 5   VIAFID ORCID Logo  ; Park, Sungjo 4   VIAFID ORCID Logo  ; Adolf, Jeffrey P 4 ; Christopher, Livia 5   VIAFID ORCID Logo  ; Hillestad, Matthew L 4 ; Bartunek, Jozef 6   VIAFID ORCID Logo  ; Atta Behfar 7   VIAFID ORCID Logo  ; Terzic, Andre 8   VIAFID ORCID Logo 

1  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA 
2  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA; Cardiovascular Division, University of Minnesota, Minneapolis, Minnesota, USA 
3  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Division of Geriatric & Gerontology Medicine, Mayo Clinic, Rochester, Minnesota, USA 
4  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA 
5  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Mayo Clinic Alix School of Medicine, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota, USA 
6  Cardiovascular Center, OLV Hospital, Aalst, Belgium 
7  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA; Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA 
8  Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA 
Pages
1320-1328
Section
ENABLING TECHNOLOGIES FOR CELL‐BASED CLINICAL TRANSLATION
Publication year
2021
Publication date
Sep 2021
Publisher
Oxford University Press
ISSN
21576564
e-ISSN
21576580
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/sctm.20-0509
ProQuest document ID
2563302069
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.