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Mesenchymal stem cell (MSC)-based tissue regeneration therapy has been extensively investigated for cardiac regeneration over the past two decades. Numerous animal and clinical investigations demonstrated the efficacy of various types of MSCs towards myocardial protection and restoration against anthracycline-induced cardiotoxicity (AIC). It has been established that local or systemic administration of MSCs considerably improved the cardiac function, while ameliorating inflammatory responses and myocardial fibrosis. Several factors influence the outcomes of MSC treatment for AIC, including MSC types, dosages, and routes and duration of administration. In this review, we discuss the recent (from 2015 to 2020) experimental and clinical research on the preventive and regeneration efficacy of different types of MSCs (with or without supporting agents) against AIC, as well as the key factors responsible for MSC-mediated cardiac repair. In addition, challenges and future perspectives of MSC-based cardiac regeneration therapy are also outlined.

[Display omitted] • Estrogen deficiency promotes M1 polarization and thus alters profiling of small extracellular vesicles (sEVs). • sEVs involve in the cross-talk between macrophages and mesenchymal stem cells. • M1-sEVs inhibit osteogenesis of mesenchymal stem cells and aggravate periodontitis. • A cluster of miR-30-5p miRNAs in M1-sEVs are predicted to inhibit osteogenesis. • Treatment of sEVs with miR-30e-5p inhibitor prevents periodontitis in OVX mice. Emerging evidence indicates that postmenopausal women with periodontitis have aggravated inflammation and prolonged course, with the detailed mechanisms largely unknown. This study aimed to determine the pathogenic role of aberrant extracellular vesicles due to imbalanced-polarized macrophages and explore the therapeutic approach for periodontitis in postmenopausal individuals. Periodontitis in ovariectomized (OVX) mouse models were established to simulate the aggravated periodontitis in postmenopausal women. Small extracellular vesicles (sEVs) derived from macrophages were isolated, characterized and tracked. Both in vitro and in vivo experiments were applied to compare the effects of M1-sEVs and M2-sEVs on osteogenesis. RNA-Seq was performed to find out up-regulated miRNAs in M1-sEVs. As data shown, compared with the Sham control mice, estrogen deficiency in the OVX-periodontitis mice, significantly increased the ratio of M1 macrophages and thus change the profile of sEVs. The sEVs could be uptaken by mesenchymal stem cells (MSCs). Furthermore, M1-sEVs inhibited the osteogenesis of MSCs and aggravated bone loss in periodontitis. Up-regulated miR-30-5p cluster were found in M1-sEVs. Prevention of the communication aberrance using miR-30e-5p inhibitor loaded sEVs in the OVX mice at least partially restores the aggravated periodontitis. Collectively, this study suggests that the increased M1-sEVs in the estrogen-deficiency context aggravate bone loss in periodontitis via negatively regulating osteogenesis of MSCs, and therapeutically targeting the process holds promise for better prognosis. [ABSTRACT FROM AUTHOR]