Stem cell–derived exosomes in the treatment of chemotherapy-induced cardiotoxicity: A systematic review of in vivo and in vitro studies

Introduction: Chemotherapy-induced cardiotoxicity (CIC) is a significant challenge in cancer treatment, with limited therapeutic options available for preventing cardiac damage. This systematic review aimed to summarize the therapeutic efficacy of stem cell–derived exosomes in CIC. Methods: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched up to April 2024, to identify relevant in vivo and in vitro studies. Two reviewers independently screened and extracted data using a pilot-tested form. The quality of the included studies was evaluated using the SYRCLE risk of bias tool for animal studies and the QUIN (QUality IN vitro) Assessment Tool. Due to heterogeneity in models, exosome sources, isolation methods, dosing, routes, timing, and outcomes, we conducted a narrative synthesis without meta-analysis. Results: Among the 107 citations obtained from the databases, 27 were included. Exosome treatment improved cardiac function parameters, including left ventricular ejection fraction (LVEF), fractional shortening (FS), and stroke volume (SV). Exosomes were associated with favorable changes in cardiac biomarker levels, including significant reductions in troponin, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Exosomes also reduced inflammation and oxidative stress markers, and ameliorated histopathological changes in cardiac tissues. They were associated with a reduction in apoptotic markers and enhanced cell survival. In addition, exosomes improved angiogenesis in daunorubicin-induced cardiac models. The available evidence suggests the beneficial effects of stem cell–derived exosomes for CIC treatment and prevention. Conclusions: Stem cell–derived exosomes demonstrate promising therapeutic effects in mitigating chemotherapy-induced cardiotoxicity by enhancing cardiac function, reducing inflammation and oxidative stress, and limiting apoptosis. These findings support the potential clinical application of exosomes as a novel, cell-free strategy for cardioprotection in cancer patients undergoing chemotherapy. Further clinical trials are warranted to confirm their efficacy and safety.