risk of arrhythmias following this procedure is reportedly high. In a recent study, researchers tested a new method that involves injecting ‘cardiac spheroids,’ cultured from human stem cells, directly into damaged ventricles. The very encouraging results observed in primate models demonstrate the potential of this approach.
The risk of arrhythmias after this procedure is said to be high. A recent study by researchers from Japan tested a new method that involves injecting ‘cardiac spheroids,’ which are cultured from human stem cells, directly into damaged ventricles. Positive outcomes were observed in primate models, showing the potential of this strategy.
Cardiovascular diseases are still a major cause of death worldwide, particularly in developed countries. Heart attacks, also known as myocardial infarctions, are increasing and result in a significant number of deaths each year.
Heart attacks typically are caused by a blockage in the coronary artery, which reduces blood flow to the heart muscle. This lack of blood flow can cause damage to the heart tissue and lead to various complications, including arrhythmias.
The heart can be damaged by various factors, leading to the death of millions of cardiac muscle cells and leaving it in a weakened state. Mammals are unable to regenerate these cells on their own, which is why heart transplants are currently the only viable option for patients with or at risk of heart failure. However, full heart transplants are costly and donors are not always readily available, prompting the medical community to seek alternative therapies.
One promising approach that has gained momentum is the use of human induced pluripotent stem cells (HiPSCs) for regenerative heart therapy. HiPSCs are cells that are derived from adult cells and reprogrammed to be similar to embryonic stem cells. This method shows potential for treating heart conditions, providing hope for those in need of effective treatments.In a recent study, a Japanese research team from Shinshu University and Keio University School of Medicine tested a new strategy for regenerative heart therapy that involves injecting ‘cardiac spheroids’ derived from mature cells that can be effectively ‘reprogrammed’ into a completely different cell type, such as cardiac muscle cells (cardiomyocytes). By transplanting or injecting cardiomyocytes derived from HiPSCs into damaged areas of the heart, it is possible to recover some lost functionality. However, previous studies have shown that this approach can increase the risk of arrythmias, which is a major obstacle for clinical trials.Myocardial infarction is a condition that occurs when the blood flow to the heart is blocked, leading to damage of the heart muscle. In a study published in the journal Circulation on April 26, 2024, a team of researchers led by Professor Yuji Shiba from Shinshu University investigated the use of induced pluripotent stem cells (iPSCs) in monkeys with myocardial infarction.
The team, which included Hideki Kobayashi and Koichiro Kuwahara from the Department of Cardiovascular Medicine at Shinshu University School of Medicine, as well as Shugo Tohyama and Keiichi Fukuda from the Department of Cardiology at Keio University School of Medicine, took a unique approach to their research. They cultured iPSCs in a specific medium that caused the cells to differentiate into a specific type of cell.The researchers extracted and purified three-dimensional clusters of cardiac cells, known as cardiac spheroids, from the cultures. They then injected around 6 × 10^7 cells into the damaged hearts of crab-eating macaques (Macaca fascicularis). Over the course of twelve weeks, they closely monitored the condition of the animals and regularly measured their cardiac function. After this, they conducted a tissue-level analysis of the monkeys’ hearts to determine whether the cardiac spheroids were capable of regenerating the damaged heart muscles.
To begin, the team confirmed that the HiPSCs had been correctly reprogrammed into cardiomyocytes.Cardiomyocytes were studied using cellular-level electrical measurements, which showed that the cultured cells exhibited potential patterns typical of ventricular cells. They also responded as expected to various known drugs. The study revealed that the cells abundantly expressed adhesive proteins like connexin 43 and N-cadherin, which would help them integrate into an existing heart’s blood vessels.
Following their production at Keio University, the cells were transported 230 km to Shinshu University. The cardiac spheroids, preserved at 4 °C in standard containers, endured the four-hour journey.y without any issues. This means that there would be no need for extremely cold temperatures when transporting the cells to clinics, making the proposed approach more affordable and easier to implement.
Lastly, the monkeys were given injections of either cardiac spheroids or a placebo directly into the damaged heart ventricle. Throughout the observation period, the researchers observed that arrythmias were very rare, with only two individuals experiencing temporary tachycardia (rapid heartbeat) in the first two weeks among the treatment group. Through echocardiography and computed tomography exams, the team verified that the hearts of monkeys that received the treatment.received treatment had improved left ventricular ejection after four weeks compared to the control group, showing better blood pumping ability.
Examination of the tissue structure showed that the cardiac grafts were fully developed and properly integrated with the existing tissue, confirming earlier findings. “Using HiPSC-derived cardiac spheroids could be an ideal method for producing cardiomyocyte products for heart regeneration, due to their simple generation process and effectiveness,” stated Assistant Professor Kobayashi. “We anticipate that this research will contribute to solving the challenge of heart regeneration.”emPulse,em as Journal of Medical Research would be very keen to report on its progress and successes in the near future.”
In conclusion, the successful development of cardiac spheroids and their application in clinical trials for cardiac regenerative therapy represent a major breakthrough in the field of cardiology. The potential to treat ventricular arrhythmia and other heart conditions using this innovative approach is truly groundbreaking. As we eagerly anticipate the results of the LAPiS trial, it is clear that the future of cardiac regenerative therapy is bright indeed.The LAPiS trial was successful, opening up new and effective treatment options for people with heart problems.
