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Nature sub-journal: Scientists successfully repair damaged pig heart

The adult heart is basically incapable of repairing damage. Compared with amphibians and fish, which can repair heart damage, mammals have limitations in repairing damaged hearts. Many heart conditions cause heart muscle cells and blood vessel cells to die and leave scar tissue that is less elastic, worsening heart function and further contributing to heart failure in people with heart disease.

On May 12, 2022, scientists from the Technical University of Munich in Germany, the Karolinska Institutet in Sweden and AstraZeneca published in Nature Cell Biology. In this study, scientists used stem cells to create a new method using human ventricular progenitor cells. (Human ventricular progenitors, HVPs) new technology to regenerate heart cells in pigs. This study confirms that HVPs are critical for organ formation during development and can become cardiac cells when needed, with the positive effect of repairing scars and damaged hearts (Figure 1) [1].

Pig hearts are physiologically very similar to human hearts, so scientists focused on the effectiveness of HVPs in repairing damaged pig hearts, providing more clues for later studies to further repair human hearts. The main research results are as follows:

1. To molecularly dissect HVPs-mediated cardiac repair at the single-cell level, scientists used an adult cardiac tissue model to simulate key steps in heart failure in vitro. Figure 2 shows that HVPs are attracted to the site of cardiac injury via CXCL12/CXCR4 signaling, where they undergo dynamic repair. The results show that HVPs can effectively promote cardiac cell regeneration by coordinating the sequential program of cardiac development;

2. To further investigate the ability of HVP to migrate and re-repair damaged myocardium in vivo, we performed HVPs transplantation in pigs ubiquitously expressing LEA29Y (LEA29Y is a human CTLA4-Ig derivative that attenuates systemic T cell responses) , after evaluation by CD68 immunoassay, it was found that there was no acute transplant rejection after transplantation. In addition, common side effects such as arrhythmia and fatal arrhythmias that patients may experience in the process of using stem cells to grow heart cells in the past were not found in this study.

Professor Karl Laugwitz from the Technical University of Munich said: "In laboratory studies, we were able to show dynamically how HVPs track damaged areas of the heart, migrate to the injury site and expertly work for heart cells, preventing the formation of scar tissue."

Dr Regina Fritsche-Danielson, research fellow at AstraZeneca, said: "The technique successfully demonstrated the formation of new tissue in the heart. More importantly, it improved cardiac function and reduced scar tissue, making it the ideal cell we have been looking for to rebuild the heart. ."

Scientists hope to conduct clinical studies in humans within the next two years, translating current research findings to develop a new treatment for human heart disease patients. If this new technology, which can repair damaged heart tissue, is successfully put into clinical use, heart disease patients may have a better life expectancy.