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Published on: January 25, 2019
Cadaveric cardiosphere-derived cells can maintain regenerative capacity and improve the heart function of
Yong Sun1,2, Di Chi1,2, Miaoxin Tan3
1a Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment , Harbin Medical University , Harbin , China.
Insights
Cardiosphere-derived cells (CDCs) harvested from cadaveric autopsy show promise for treating non-ischemic cardiomyopathy. These cells maintain their function and improve heart function after transplantation.
Area of Science:
- Regenerative Medicine
- Cardiology
- Cell Biology
Background:
- Cardiosphere-derived cells (CDCs) are effective in treating cardiomyopathy but are typically sourced from myocardial biopsies.
- The potential of utilizing cadaveric autopsy specimens for CDC generation remains unexplored.
Purpose of the Study:
- To investigate the feasibility of obtaining functional CDCs from cadaveric autopsy specimens.
- To assess the characteristics and therapeutic potential of cadaveric CDCs in non-ischemic cardiomyopathy models.
Main Methods:
- Human and mouse cadaveric cardiac tissues were cultured to generate CDCs (CLH-EDCs and CM-CDCs).
- CDC proliferation, differentiation, and paracrine effects were evaluated.
- Cadaveric CM-CDCs were transplanted into a rat model of doxorubicin-induced dilated cardiomyopathy (DCM).
Main Results:
- CDC yield decreased with extended post-mortem time, but cells retained viability and function.
- Transplantation of cadaveric CM-CDCs improved left ventricular ejection fraction and reduced cardiac remodeling in the DCM model.
- Cells cultured from 24-hour post-mortem specimens showed comparable paracrine function to those from 0-hour specimens.
Conclusions:
- Cadaveric autopsy is a viable source for generating proliferative and differentiative CDCs.
- Cadaveric CDCs hold potential for allograft transplantation to treat non-ischemic cardiomyopathy.
- These cells can reduce myocardial fibrosis, attenuate left ventricular remodeling, and improve cardiac function.
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.
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.
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).
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.
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