Many people live with undiagnosed cardiac arrythmia, with estimates ranging from 1.5% to 5% of the population¹, which equates (in the US alone) to approximately 5-17 million people. Regardless of the exact statistics, the numbers are increasing with average population age. Severe arrythmias can be life-threatening, so researchers continue to develop new technologies and regenerative medicines to better support this increasing need.

Unfortunately, technological pacemakers have limitations such as inability to grow with pediatric patients, inability to adapt to changing neurophysiologic conditions inherent in mammalian biology, potential electromagnetic interference with device operation, short battery life, etc. As a result, researchers are turning to biological methods of restoring cardiac rhythm.

Cardiac Conduction System

In normal mammalian biology, cardiac-contraction electrical signals propagate in the following sequence: sinoatrial node (the heart’s natural pacemaker), atrioventricular node, bundle of His, left and right bundle branches, and finally the Purkinje fibers.²

Cardiac Regeneration

Despite the futuristic appearance of a biological rather than electronic solution, the first attempts were actually made a century ago when (due to the order listed above) research began in animal models via transplanting (auto- or xenografting) right atrial segments containing sinoatrial node into ventricular tissue. These grafts were able to reestablish seminormal cardiac rhythm in a matter of hours, but began to fibrose, and degraded to nonfunctional in a matter of days,³ thereby establishing precedent for success, once surgical and biological understanding had sufficiently advanced.

Gene Therapy

Modern technology has contributed greatly to our understanding of those early attempts. Stem cell differentiation, gene therapy and engineering have advanced our in vitro and in vivo trials of resetting cardiac cell rhythms in a variety of models, from canine-to-canine, to human-to-porcine.  

Recent advances have gone down to the sub-tissue level, harvesting canine fetal atrial sinoatrial cells and injecting them into the myocardial wall of the right ventricle of an adult canine after complete heart block. The procedure was able to reengage cardiac rhythm, though atypical.⁴

Later, a similar procedure was performed injecting human cells into a porcine model. The human cells were able to properly reset and pace cardiac rhythm as well as establish correct autonomic response between donor and host cells.⁵

More recent experiments have relied on the nearly unlimited differentiation power of pluripotent stem cells. Modern research has allowed researchers to guide the cells into cardiac-specific differentiation, but the human heart itself is composed of a wide variety of cells, and procedures have so far tended to produce a mixture of these types, so finer differentiation control is still needed.²

Gene therapy is rising quickly to the forefront, with multiple experiments over the last 25 years showing promise. Dual synthetic genes were transduced into the left bundle branches of canine models after heart block, which restored rate and rhythm.²

In the same experimental circumstances, inducing overexpression of certain genes in the left bundle branch also restored rhythm but with a greater sensitivity to autonomic regulation. Furthermore, viral vectors have been used to transform myocardial cells into pacemaking cells.²

Transonic’s devices are involved in many cardiovascular surgeries, so we applaud the efforts of every researcher and physician who is working for a better cardiac-care future, and we look forward to the day when many cardiac problems, not only pacemakers, can be replaced with their autologous analogues.

References:

1. Arrhythmia: Symptoms & Treatment
2. Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration - PMC
3. Rylant P. (1927). Contribution à l'ètude de l'automatisme et de la conduction dans le coeur, in Bulletin de l'Académie royale de médecine de Belgique (Bulletin de l'Académie royale de médecine de Belgique: ), 161–200.
4. Implantation of Sinoatrial Node Cells Into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate - PMC
5. Biological pacemaker created by fetal cardiomyocyte transplantation - PubMed