The human fetal and adult stem cell secretome can exert cardioprotective paracrine effects against cardiotoxicity and oxidative stress from cancer treatment

Federico Villa, Silvia Bruno, Ambra Costa, Mingchuan Li, Michele Russo, James Cimino, Paola Altieri, Clarissa Ruggeri, Cansu Gorgun, Pierangela De Biasio, Dario Paladini, Domenico Coviello, Rodolfo Quarto, Pietro Ameri, Alessandra Ghigo, Silvia Ravera, Roberta Tasso, Sveva Bollini

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotox-icity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been docu-mented. 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 cardiopro-tective 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 cardiomy-ocytes (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.

Original languageEnglish
Article number3729
JournalCancers
Volume13
Issue number15
DOIs
Publication statusPublished - Aug 1 2021

Keywords

  • Cancer treatment
  • Cardiomyocyte
  • Cardiotoxicity
  • Doxorubicin
  • Mitochondria
  • Oxidative stress
  • Paracrine effect
  • Stem cell

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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