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Updated: Aug 19, 2025
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Normothermic Ex Vivo Heart Perfusion with Mesenchymal Stem Cell-Derived Conditioned Medium Improves Myocardial Tissue
Zifeng Zeng1, Liwei Xu1, Yu Xu1
1Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China.
Insights
Bone marrow mesenchymal stem cells-conditioned medium (CM) combined with normothermic ex vivo heart perfusion (EVHP) alleviates warm ischemia/reperfusion (I/R) injury in donation after circulatory death (DCD) hearts. This approach reduces oxidative stress, inflammation, and apoptosis, potentially increasing the donor heart supply.
Area of Science:
- Cardiology
- Regenerative Medicine
- Transplantation Immunology
Background:
- Donation after circulatory death (DCD) hearts offer a potential solution to donor organ shortages.
- However, DCD hearts are susceptible to significant warm ischemia/reperfusion (I/R) injury.
- Bone marrow mesenchymal stem cells-conditioned medium (BMSCs-CM) has shown promise in mitigating organ I/R injury.
Purpose of the Study:
- To investigate the efficacy of normothermic ex vivo heart perfusion (EVHP) combined with BMSCs-CM in preserving DCD hearts.
- To assess the impact of this combined treatment on reducing myocardial warm I/R injury.
Main Methods:
- Donor rats were divided into DCD-Control and DCD-CM groups.
- Hearts underwent a 25-minute warm ischemia period followed by 105 minutes of normothermic EVHP.
- BMSCs-CM or vehicle was added to the perfusate; cardiac function was monitored.
Main Results:
- BMSCs-CM contained bioactive factors targeting apoptosis, inflammation, and oxidative stress.
- DCD hearts exhibited increased oxidative stress, inflammation, and apoptosis compared to controls.
- CM treatment improved left ventricular developed pressure and attenuated injury markers.
Conclusions:
- Normothermic EVHP with BMSCs-CM effectively alleviates warm I/R injury in DCD hearts.
- This strategy reduces oxidative stress, inflammation, and apoptosis.
- The findings suggest a potential method to expand the donor heart pool by utilizing DCD hearts.
Objective:
Adopting hearts from donation after circulatory death (DCD) is a promising approach to enlarge the donor pool. Nevertheless, DCD hearts experience severe warm ischemia/reperfusion (I/R) injury. Recent studies have demonstrated that conditioned medium (CM) derived from bone marrow mesenchymal stem cells (BMSCs) has the potential of reducing organ I/R injury. Therefore, we investigated whether DCD heart preservation with normothermic ex vivo heart perfusion (EVHP) and BMSCs-CM treatment could alleviate myocardial warm I/R injury in the DCD hearts.
Methods:
We randomly divided donor rats into two groups: (1) DCD-Control group and (2) DCD-CM group. Before DCD heart preservation with the normothermic EVHP system for 105 minutes, rats suffered from a 25-minute warm ischemia injury in the DCD procedure. Vehicle or CM (300 μl) was added to the perfusate at the beginning of the perfusion process. The cardiac function of DCD hearts in the DCD-Control and DCD-CM groups was measured every 30 minutes. Besides, non-DCD hearts were harvested from the beating-heart rats.
Results:
The antibody array demonstrated that the CM contained 14 bioactive factors involved in apoptosis, inflammation, and oxidative stress. Warm ischemia injury resulted in a significant increase in the level of oxidative stress, inflammation, and apoptosis in the DCD hearts of DCD-Control group. Furthermore, compared with the DCD-Control group, CM treatment increased the developed pressure, dP/dtmax and dP/dtmin of the left ventricular in the DCD hearts during a 90-minute EVHP. Moreover, the administration of CM attenuated the level of oxidative stress, inflammation, and apoptosis in the DCD hearts of the DCD-CM group.
Conclusions:
Normothermic EVHP combined with CM treatment can alleviate warm I/R injury in the DCD hearts by decreasing the level of oxidative stress, inflammatory response, and apoptosis, which might alleviate the shortage of donor hearts by adopting DCD hearts.
