Cadaveric cardiosphere-derived cells can maintain regenerative capacity and improve the heart function of cardiomyopathy

尸体心脏球衍生细胞可维持再生能力并改善心肌病的心脏功能

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作者:Yong Sun, Di Chi, Miaoxin Tan, Kai Kang, Maomao Zhang, Xiangyuan Jin, Xiaoping Leng, Rui Cao, Xianglan Liu, Bo Yu, Jian Wu

Conclusion

CDCs from cadaveric autopsy are highly proliferative and differentiative, and may be used as a source for allograft transplantation, in order to decrease myocardial fibrosis, attenuate left ventricular remodeling, and improve heart function in doxorubicin-induced non-ischemic cardiomyopathy.

Methods

Cardiac tissues from human or mouse cadavers were harvested, plated at 4°C, and removed at varying time points to culture human CDCs (CLH-EDCs) and mouse CDCs (CM-CDCs). The differentiation and paracrine effects of CDCs were also assessed. Furthermore, intramyocardial injection of cadaveric CM-CDCs was performed in an induced dilated cardiomyopathy (DCM) model.

Objective

Cardiosphere-derived cells (CDCs) improve cardiac function and attenuate remodeling in ischemic and non-ischemic cardiomyopathy, and are currently obtained through myocardial biopsy. However, there is not any study on whether functional CDCs may be obtained through cadaveric autopsy with similar benefits in non-ischemic cardiomyopathy.

Results

With the extension of post mortem hours, the number of CLH-EDCs and CM-CDCs harvested from autopsy specimens decreased. The expressions of von Willebrand factor (VWF) and smooth muscle actin (SMA) on CDCs were gradually reduced, however, cardiac troponin I (TNI) expression increased in the 24 h group compared to the 0 h group. CLH-EDCs were also found to have similar paracrine function in the 24 h group compared to 0 h group. 8 weeks after CM-CDCs transplantion to the injured heart, mean left ventricular ejection fraction increased in both 0 h (64.99 ± 3.4%) and 24 h (62.99 ± 2.8%) CM-CDCs-treated groups as compared to the PBS treated group (53.64 ± 5.6 cm), with a decrease in left ventricular internal diastolic diameter (0.29 ± 0.08 cm and 0.32 ± 0.04 cm in 0 h and 24 h groups, vs. 0.41 ± 0.05 cm in PBS group).

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