{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:44Z","timestamp":1787027744556,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T00:00:00Z","timestamp":1627084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["Young Investigator Grant\u2014GR-2013-02357519"],"award-info":[{"award-number":["Young Investigator Grant\u2014GR-2013-02357519"]}]},{"name":"University of Genova, Genova, Italy","award":["\u201cCuriosity Driven\u201d grant: Triggering CARDIOmyocyte renewal by harnessing STem cell pARacrine potential (CARDIO-STAR)"],"award-info":[{"award-number":["\u201cCuriosity Driven\u201d grant: Triggering CARDIOmyocyte renewal by harnessing STem cell pARacrine potential (CARDIO-STAR)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotoxicity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been documented. We demonstrated that the human fetal amniotic fluid-stem cell (hAFS) secretome, namely the secreted paracrine factors within the hAFS-conditioned medium (hAFS-CM), exerts pro-survival effects on Dox-exposed cardiomyocytes. Here, we provide a detailed comparison of the cardioprotective potential of hAFS-CM over the secretome of mesenchymal stromal cells from adipose tissue (hMSC-CM). hAFS and hMSC were preconditioned under hypoxia to enrich their secretome. The cardioprotective effects of hAFS\/hMSC-CM were evaluated on murine neonatal ventricular cardiomyocytes (mNVCM) and on their fibroblast counterpart (mNVFib), and their long-term paracrine effects were investigated in a mouse model of Dox-induced cardiomyopathy. Both secretomes significantly contributed to preserving mitochondrial metabolism within Dox-injured cardiac cells. hAFS-CM and hMSC-CM inhibited body weight loss, improved myocardial function, reduced lipid peroxidation and counteracted the impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis induced by Dox. The hAFS and hMSC secretomes can be exploited for inhibiting cardiotoxic detrimental side effects of Dox during cancer therapy, thus ensuring cardioprotection via combinatorial paracrine therapy in association with standard oncological treatments.<\/jats:p>","DOI":"10.3390\/cancers13153729","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:06:21Z","timestamp":1627250781000},"page":"3729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment"],"prefix":"10.3390","volume":"13","author":[{"given":"Federico","family":"Villa","sequence":"first","affiliation":[{"name":"Cellular Oncology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambra","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Cimino","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Altieri","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Biology, Department of Internal Medicine (DIMI), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Biology, Department of Internal Medicine (DIMI), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0460-2952","authenticated-orcid":false,"given":"Cansu","family":"Gorgun","sequence":"additional","affiliation":[{"name":"Cellular Oncology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangela","family":"De Biasio","sequence":"additional","affiliation":[{"name":"Unit of Prenatal Diagnosis and Perinatal Medicine, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Paladini","sequence":"additional","affiliation":[{"name":"Fetal Medicine and Surgery Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-865X","authenticated-orcid":false,"given":"Domenico","family":"Coviello","sequence":"additional","affiliation":[{"name":"Human Genetics Laboratory, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-894X","authenticated-orcid":false,"given":"Rodolfo","family":"Quarto","sequence":"additional","affiliation":[{"name":"Cellular Oncology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Ameri","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Biology, Department of Internal Medicine (DIMI), University of Genova, 16132 Genova, Italy"},{"name":"Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-5296","authenticated-orcid":false,"given":"Alessandra","family":"Ghigo","sequence":"additional","affiliation":[{"name":"Department of 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