Progress Towards Cardiomyocyte Cell Therapy for the Injured Heart
Researchers here demonstrate an approach to cell therapy for an injured heart that produces lesser degrees of abnormal function than prior efforts. There has been some concern that delivering new cells to the heart to spur greater regeneration will disrupt the electrical regulation of heartbeats, as animal studies suggested an unacceptable risk of arrhythmia following treatment. This work still makes use of cardiomyocytes generated from induced pluripotent stem cells, already accomplished by a number of other groups, but differences in the details of the approach appear to make a positive change in the outcome.
In a recent study, a research team tested a new strategy for regenerative heart therapy that involves injecting 'cardiac spheroids' derived from human induced pluripotent stem cells (HiPSCs) into monkeys with myocardial infarction. First, the team verified the correct reprogramming of HiPSCs into cardiomyocytes. They observed, via cellular-level electrical measurements, that the cultured cells exhibited potential patterns typical of ventricular cells. The cells also responded as expected to various known drugs. Most importantly, they found that the cells abundantly expressed adhesive proteins such as connexin 43 and N-cadherin, which would promote their vascular integration into an existing heart. Afterwards, the cells were transported from the production facility. The cardiac spheroids, which were preserved at 4°C in standard containers, withstood the four-hour journey without problem. This means that no extreme cryogenic measures would be needed when transporting the cells to clinics, which would make the proposed approach less expensive and easier to adopt.
Finally, the monkeys received injections of either cardiac spheroids or a placebo directly into the damaged heart ventricle. During the observation period, the researchers noted that arrythmias were very uncommon, with only two individuals experiencing transient tachycardia (fast pulse) in the first two weeks among the treatment group. Through echocardiography and computed tomography exams, the team confirmed that the hearts of monkeys that received treatment had better left ventricular ejection after four weeks compared to the control group, indicating a superior blood pumping capability. Histological analysis ultimately revealed that the cardiac grafts were mature and properly connected to pre-existing existing tissue. "The favorable results obtained thus far are sufficient to provide a green light for our clinical trial. We are already employing the same cardiac spheroids on patients with ischemic cardiomyopathy."
Link: https://www.shinshu-u.ac.jp/english/topics/2024/04/using-stem-cell-deri.html