Work

Novel Allogeneic Mitochondria and Associated Organelle Complex Treatment Prevents Myocardial Ischemia-Reperfusion Injury Through Anti-Apoptotic Effects

Year: 2025

Type: article

Abstract: BACKGROUND: Ischemia-reperfusion (I/R) injury can damage mitochondria and lead to cardiomyocyte apoptosis. Freshly prepared autologous mitochondria have shown benefits against I/R injury, but it remains unclear whether allogeneic mitochondrial organelle complex Q (MRC-Q) after freeze-thawing can also be effective in this context. OBJECTIVES: This study aimed to determine whether administering MRC-Q can protect the heart from ischemia I/R injury in animal models. METHODS: The MRC-Q used in our current experiments was intactly isolated by proprietary technology and cryopreserved. A mouse and porcine model of cardiac I/R injury was employed. In vitro experiments were performed using H9C2 cardiomyocytes subjected to hypoxic-reoxygenation conditions. RESULTS: Our initial study demonstrated that MRC-Q can be storable with a maintenance of adenosine triphosphate production capacity. Next, we tested cardioprotective effects of MRC-Q administration on I/R injury in a murine model. Compared to the vehicle group, the MRC-Q-treated group showed a reduction in infarct size with fewer apoptotic cells, a decrease in circulating cardiac enzymes, and an improvement in cardiac function. In vitro studies revealed that MRC-Q was taken up into cardiomyocyte cells in a time-dependent manner. Next, we demonstrated that cell viability was improved in the MRC-Q-treated group after hypoxia/reoxygenation. Further examinations suggested that one of the mechanisms of cardioprotection by MRC-Q could be mediated by the secretion of mitochondria-derived peptides, which could inhibit apoptosis-promoting signals. In addition, MRC-Q augmented endogenous mitochondrial quality control in injured myocytes followed by up-regulation of adenosine triphosphate production and anti-reactive oxygen species activity. Finally, a preclinical pig model also confirmed the cardioprotective effects of MRC-Q administration. CONCLUSIONS: Our data demonstrated that freeze-thawed MRC-Q have a protective effect on the heart after I/R injury.

Source: JACC Asia

DOI: 10.1016/j.jacasi.2025.09.022