Adoptive transfer of M2-like macrophages significantly improved cardiac function and attenuated cardiac fibrosis and cardiomyocyte apoptosis in doxorubicin-induced heart failure.
Does M2-like macrophage transplantation improve cardiac function in doxorubicin-induced heart failure in mice?
Adoptive transfer of M2-like macrophages protects against doxorubicin-induced cardiotoxicity in mice, potentially via mitochondrial transfer.
AIMS: The alternatively activated macrophages have shown a cardioprotective effect in heart failure. However, the effect of M2 adoptive transfer in non-ischemic heart failure is unknown. In this study, we evaluated the efficacy of M-CSF plus IL-4 induced M2-like macrophages transplantation in doxorubicin-induced cardiotoxicity. METHODS: M2-like macrophages by a combination of M-CSF plus IL-4 treatment. C57BL/6 mice received a single intraperitoneal injection of doxorubicin (15 mg/kg). The treatment group were treated with M2-like macrophages (1 × 10⁶ cells per mouse; i. v. ) once a week for 2 weeks. After 3 weeks, we examined the percentage of resident cells and cardiac function. Furthermore, we evaluated cardiac fibrosis, cardiomyocyte apoptosis and circulating inflammatory factors. Finally, we investigated the mitochondria transfer in vitro in a direct and indirect co-culture conditions. RESULTS: Cardiac function was significantly improved in doxorubicin-induced heart failure by adoptive transfer of M2-like macrophages. Besides, M2-like macrophages treatment attenuated cardiac fibrosis and cardiomyocyte apoptosis, as well as increased the level of circulating IL-4 and Th2 response. In vitro, M2-like macrophages could transfer mitochondria to injured cardiomyocytes in a direct and indirect way. CONCLUSIONS: In our study, adoptive transfer of M2-like macrophages could protect against the doxorubicin-induced cardiotoxicity, which may be partly attributed to mitochondria transfer. And M2-like macrophages transplantation could become a treatment for non-ischemic heart failure in the clinical practice.
Liu et al. (2022) studied Doxorubicin-induced cardiotoxicity / heart failure. M2-like macrophages transplantation was evaluated on Cardiac function. Adoptive transfer of M2-like macrophages significantly improved cardiac function and attenuated cardiac fibrosis and cardiomyocyte apoptosis in doxorubicin-induced heart failure.