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@article{Constantinou:2020:10.1038/s41598-020-69495-w,
author = {Constantinou, C and Miranda, Almeida A and Chaves, Guerrero P and Bellahcene, M and Massaia, A and Cheng, K and Samari, S and Rothery, S and Chandler, A and Schwarz, R and Harding, S and Punjabi, P and Schneider, MD and Noseda, M},
doi = {10.1038/s41598-020-69495-w},
journal = {Scientific Reports},
title = {Human pluripotent stem cell-derived cardiomyocytes as a targetplatform for paracrine protection by cardiac mesenchymal stromalcells},
url = {http://dx.doi.org/10.1038/s41598-020-69495-w},
volume = {10},
year = {2020}
}
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TY  - JOUR
AB  - Ischemic heart disease remains the foremost cause of death globally, with survivors at risk for subsequent heart failure. Paradoxically, cell therapies to offset cardiomyocyte loss after ischemic injury improve long-term cardiac function despite a lack of durable engraftment. An evolving consensus, inferred preponderantly from non-human models, is that transplanted cells benefit the heart via early paracrinesignals. Here, we tested the impact of paracrine signals on human cardiomyocytes, using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as the target of mouse and human cardiac mesenchymal stromal cells (cMSC) with progenitor-like features. In co-culture and conditioned medium studies, cMSCs markedly inhibited human cardiomyocyte death. Little or no protection was conferred by mouse tail tip or human skin fibroblasts. Consistent with the results of transcriptomic profiling, functional analyses showed that the cMSC secretome suppressed apoptosis and and preserved cardiac mitochondrial transmembrane potential. Protection was independent of exosomes under the conditions tested. In mice, injecting cMSC-conditioned media into the infarct border zone reduced apoptotic cardiomyocytes >70% locally. Thus, hPSC-CMs provide an auspicious, relevant human platform to investigate extracellular signals for cardiac muscle survival, substantiating human cardioprotection by cMSCs, and suggesting the cMSC secretome or its components as potential cell-free therapeutic products.
AU  - Constantinou,C
AU  - Miranda,Almeida A
AU  - Chaves,Guerrero P
AU  - Bellahcene,M
AU  - Massaia,A
AU  - Cheng,K
AU  - Samari,S
AU  - Rothery,S
AU  - Chandler,A
AU  - Schwarz,R
AU  - Harding,S
AU  - Punjabi,P
AU  - Schneider,MD
AU  - Noseda,M
DO  - 10.1038/s41598-020-69495-w
PY  - 2020///
SN  - 2045-2322
TI  - Human pluripotent stem cell-derived cardiomyocytes as a targetplatform for paracrine protection by cardiac mesenchymal stromalcells
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-020-69495-w
UR  - http://hdl.handle.net/10044/1/80671
VL  - 10
ER  -
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