Cardiac Nestin+ Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells

Dilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease of the heart muscle; however, the etiology and pathogenesis of DCM were still poorly understood. Nestin has been reported a spe- cial marker of stem/progenitor cells in various tissues, and the tissue resident Nestin+ cells could promote the wound healing and tissue remodeling. However, it remains unclear whether Nestin+ cells participate in the pro- tection of cardiomyocytes during the pathogenesis of DCM. Here the model of mice DCM was induced by dox- orubicin (DOX) intraperitoneal injection and observed heart failure and ventricular enlargement via echocar- diography and histologic analysis, respectively. During DCM pathogenesis, the number of Nestin+ cells showed a significant peak on day 6 after DOX treatment, which then gradually decreases to lower than normal levels af- ter day 30 in the total population of the heart. Furthermore, we found that the isolated increased heart-derived Nestin+ cells are mesenchymal property and could protect DOX-induced HL-1 cells toxicity in vitro by promot- ing their proliferation and inhibiting their apoptosis. Collectively, our results showed that Nestin+ cells increased during DCM pathogenesis and played an important role in protecting against the DOX-induced HL-1 cells loss via regulating proliferation and apoptosis. Thus, the loss of Nestin+ cells might be an etiology to DCM patho- genesis, and these cells could be a promising candidate cell source for study and treatment of DCM patients.