Specialized cells that keep the heart beating have the ability to regenerate after birth, study finds
The specialized cells that conduct electricity to maintain the heartbeat have a previously unknown ability to regenerate within days of birth, suggests a new study in mice by researchers at UT Southwestern. The discovery, published online in the Journal of Clinical Investigation, could potentially lead to treatments for cardiac arrhythmias that avoid the need for pacemakers or invasive drugs by encouraging the heart to heal itself instead.
Patients with arrhythmia don’t have many great options. Our results suggest that one day we may be able to induce regeneration of the heart itself to treat these conditions.. “
Nikhil V. Munshi, MD, PhD, Study Leader and Cardiologist and Associate Professor of Internal Medicine, Molecular Biology, UT Southwestern Medical Center
Munshi is also Associate Professor at the Eugene McDermott Center for Human Growth and Development
Dr. Munshi studies the cardiac conduction system, an interconnected system of specialized heart muscle cells that generate electrical impulses and transmit those impulses to make the heart beat. Although studies have shown that non-conductive heart muscle cells have some capacity for regeneration for a limited time after birth – with many discoveries in this area led by scientists at UTSW – it was largely believed that Conductive cells called nodal cells lost this ability during the fetal period.
Previous research had suggested that neonatal ganglion cells lose their qualities as stem cells before birth, giving them negligible regenerative properties. However, Dr Munshi explained, their regeneration abilities had never been directly tested because there was no way to remove only nodal cells in animal models to stimulate regeneration.
To solve this problem, Dr Munshi and his colleagues used genetic engineering to develop mice whose atrioventricular (AV) ganglion cells, located near the intersection of the four chambers of the heart, died when fed. with tamoxifen, a breast cancer medicine. In adult mice of this strain that received tamoxifen, tissue samples and EKGs revealed progressive cardiac damage resulting in AV node cell death over the following weeks and months. However, when newborn mice were treated, heart function appeared to be completely normal in a third of the animals about a month later.
On a closer look, the researchers performed EKGs on newborn mouse models of AV lymph node failure every other day after tamoxifen treatment. These tests revealed an initial injury to the heart which gradually healed in many animals. Although examination of the tissues showed that this healing did not result in a completely normal heart in adulthood, it was enough for the mice to have a regular heartbeat.
Oddly enough, further investigation showed that non-muscle heart cells were the predominant cell type that proliferated after nodal cell death. These cells appeared to modulate the production of proteins that help heart cells make electrical connections.
Why these proteins increased and why only about a third of animals showed regeneration remains unclear, Dr Munshi said. He and his colleagues plan to continue to study the molecular mechanisms behind this phenomenon to gain more knowledge that could eventually lead to a drug capable of stimulating the regeneration pathway on demand to regrow damaged lymph nodes in patients with arrhythmia. .
UT Southwestern Medical Center
Wang, L., et al. (2021) Inducible damage to cardiomyocytes in the atrioventricular conduction system reveals latent regenerative capacity in mice. The Journal of Clinical Investigation. doi.org/10.1172/JCI138637.