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

doi:10.1002/sctm.20-0509

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

Cardiovascular Medicine

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	1320-1328
Number of pages	9
Journal	Stem Cells Translational Medicine
Volume	10
Issue number	9
DOIs	https://doi.org/10.1002/sctm.20-0509
State	Published - Sep 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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10.1002/sctm.20-0509

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Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome. / Arrell, D. Kent; Crespo-Diaz, Ruben J.; Yamada, Satsuki; Jeon, Ryounghoon; Garmany, Armin; Park, Sungjo; Adolf, Jeffrey P.; Livia, Christopher; Hillestad, Matthew L.; Bartunek, Jozef; Behfar, Atta ; Terzic, Andre.

In: Stem Cells Translational Medicine, Vol. 10, No. 9, 09.2021, p. 1320-1328.

Research output: Contribution to journal › Article › peer-review

Arrell, D. Kent ; Crespo-Diaz, Ruben J. ; Yamada, Satsuki ; Jeon, Ryounghoon ; Garmany, Armin ; Park, Sungjo ; Adolf, Jeffrey P. ; Livia, Christopher ; Hillestad, Matthew L. ; Bartunek, Jozef ; Behfar, Atta ; Terzic, Andre. / Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome. In: Stem Cells Translational Medicine. 2021 ; Vol. 10, No. 9. pp. 1320-1328.

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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.",

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

note = "Funding Information: The authors recognize Mayo Clinic Genome Analysis, Proteomics, and Bioinformatics Cores. Authors thank Jonathan J. Nesbitt for mouse surgeries; Christian S. Rosenow for proteomic sample preparation; Katrina M. Tollefsrud, Kristin W. O'Meara, and Diane M. Jech for echocardiography analysis; Lois A. Rowe and Ryan C. Mahlberg for histology. This work was supported by National Institutes of Health (R01 HL134664, T32 GM 65841), Marriott Family Foundation, Van Cleve Cardiac Regenerative Medicine Program, Michael S. and Mary Sue Shannon Family, Mayo Clinic Center for Regenerative Medicine, and Medical Scientist Training Program at Mayo Clinic. Publisher Copyright: {\textcopyright} 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.",

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AU - Garmany, Armin

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AU - Livia, Christopher

AU - Hillestad, Matthew L.

AU - Bartunek, Jozef

AU - Behfar, Atta

AU - Terzic, Andre

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Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome

Abstract

Keywords

ASJC Scopus subject areas

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