Throughout life each heart beat is regulated primarily by a specialized tissue called the sinoatrial node. Unfortunately, this natural pacemaker’s ability to maintain the heart rate properly can be disrupted by a number of issues including congenital defects, aging, or ischemic heart disease. Recent work produced by researchers in Dr. Gordon Keller’s lab at the University of Toronto may lead to new therapies based on natural pacemaker cells grown in the lab. These human pacemaker-like cells had the ability to generate electricity spontaneously and were able to pace a rat heart after being implanted for 2 weeks.
To create this specialized cell type, they took a developmental biology approach by changing the cell culture conditions with the same small molecules and proteins that developing pacemaker cells encounter in the embryo. After careful tuning, the human stem cells were transformed into an enriched population of the desired human pacemaker cells. This is exciting because other sources of progenitor cells have been genetically-engineered to overexpress a potent cancer gene. The final cells derived in this work are a closer match to “real” pacemaker cells and are safer for clinical use.
After verifying that the cells displayed proper bioelectric behaviors in the Petri dish, the researcher took the project one step further by injecting the cells directly into a rat heart. Implanted pacemaker cells were shown to not only connect with the host cells by sharing hollow proteins that allow ions to flow in and out between the cells to pass electric signals, but the human pacemaker cells were able to pace the rat’s own ventricular cells.
Electronic pacemakers, although they have been unquestionably an essential life-sustaining device for thousands of patients, suffer from a number of drawbacks including: the inability to adapt/grow to changes in the heart (particularity important for pediatric patients), potential risk of infection after implantation, limited battery life, and even failure due to electromagnetic interference.
This work presents the exciting possibility that one day patients in need of pacemaker treatment could receive an injection of lab-grown pacemaker cells that could serve as a life-long cure, avoiding the need to implant an electronic pacemaker. Next steps will likely involve testing in the sinoatrial node of rodents and eventually moving to large animal models such as the pig.
Here’s video of in-vitro demonstration of the stem cell-derived pacemaker heart cells:
Study in Nature Biotechnology: Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker…