Human umbilical cord blood derived stem cells repair doxorubicin-induced pathological cardiac hypertrophy in mice

Abstract

In the present study, we investigated the cardiomyogenic potential of human umbilical cord blood (hUCB)-derived stem cells and whether stem cell treatment repairs the pathological hypertrophy induced by doxorubicin (DOX) in cultured neonatal rat cardiomyocytes (NRCM) and in mouse hearts. hUCB, which were labeled with cell tracker dye, were co-cultured with isolated NRCM in vitro. After 48 h of incubation, the red stained hUCB cells (30%) contracted rhythmically and synchronously (physical examination). These differentiated hUCB also expressed cardiac specific α-actinin and showed diffused expression of connexin 43 and N-cadherin, thereby suggesting a tight electrical coupling among hUCB cells and myocytes. When co-cultured, hUCB also reversed the pathological effects induced by DOX in NRCM and in mice as seen by RT-PCR, immunoblot analysis and immunocytochemistry. hUCB migrated and integrated into the hearts of mice that were treated with DOX after intravenous injection and reversed the expression of pathological hypertrophic markers induced by DOX in mice. Further, we observed a shift from pathological hypertrophy towards physiological hypertrophy by hUCB in DOX-challenged mice. hUCB treatment in mice decreased DOX-induced increase of heart weight to body mass ratio and fibrosis. Taken together, these findings suggest the potential therapeutic use of hUCB in reversing heart failure conditions.