Transplantation of engineered heart tissue as a biological cardiac assist device for treatment of dilated cardiomyopathy

摘要

AimThe aim of this study was to characterize an alternative treatment for dilated cardiomyopathy (DCM) using a novel cardiac biological assist device created from engineered heart tissue (EHT).Methods and resultsThe EHTs were constructed in vitro from matrigel, collagen, and neonatal rat cardiomyocytes as small ring-like spontaneously contracting devices. DCM was induced in 50 rats by 6 weeks doxorubicin treatment (2.5 mg/kg/week). After 38 drug-free days, rats underwent either implantation of EHT (DCM-EHT, n = 13), which was sutured around the ventricles, or sham operation (DCM-Sham, n = 12). Eleven untreated healthy rats served as the control group. Rats were investigated using a Millar catheter for pressure-volume loop recording, and by echocardiography 30 days after operation. Thereafter, the hearts were excised and investigated functionally, histologically, and biochemically. Doxorubicin led to the development of DCM with reduced fractional shortening (FS), reduced dP/dt max, increased systolic and diastolic LV diameters, and reduced response to dobutamine. In DCM-Sham, these changes were further enhanced, while in DCM-EHT we found improved FS, dP/dtmax, and dobutamine responsiveness. In isolated hearts, electrical multielectrode mapping revealed that EHT was electrically activated synchronously to the recipient heart. Histologically, we found increased vascularization in the EHT and the recipient heart, and EHT vessels connected to the coronary system.ConclusionsImplantation of EHT improves LV performance in rats with doxorubicin-induced DCM.