A joint research team from Shinshu University and Keio University School of Medicine in Japan tested a novel strategy for heart regeneration by injecting human-induced pluripotent stem cell (HiPSC)-derived cardiac spheres (three-dimensional clusters of heart cells) into monkeys with myocardial infarction, observing promising results. The related study was published on April 26th in the journal "Circulation."
Transplanting myocardial cells into damaged areas of the heart to restore lost function is a form of heart regeneration therapy. However, the risk of postoperative arrhythmias is currently very high.
Researchers cultured HiPSCs in a medium to differentiate them into myocardial cells, extracted and purified cardiac spheres, and then injected approximately 6×107 cells into the damaged hearts of crab-eating macaques. They monitored the monkeys for 12 weeks, regularly measuring their heart function. Subsequently, they analyzed the monkey hearts at a tissue level to assess whether the cardiac spheres could regenerate the damaged myocardium.
Initially, the team validated the correct reprogramming of HiPSCs into myocardial cells. They observed at the cellular level through electrophysiological measurements that the cultured cells exhibited typical ventricular cell electrical patterns. These cells also responded as expected to various known drugs. The cells expressed a large amount of adhesion proteins, aiding in their vascular integration into the existing heart.
Subsequently, these cells were transported from Keio University to Shinshu University, 230 kilometers away. The cardiac spheres stored in standard containers at 4°C could easily withstand the 4-hour journey, indicating that extreme low-temperature measures are unnecessary when transporting cells to medical facilities.
Finally, monkeys received direct injections of cardiac spheres or placebos into the damaged ventricles. Arrhythmias were very rare during the observation period. In the first two weeks of the treatment group, only two monkeys experienced brief episodes of tachycardia. Through echocardiography and computed tomography scans, the research team confirmed that, compared to the control group, the monkeys' left ventricular ejection was better after 4 weeks in the treatment group, indicating improved blood pumping capacity.
Histological analysis ultimately demonstrated that the transplanted hearts had matured and correctly integrated with the original tissue, consolidating the previously observed results.
