Cardiac regeneration: a new electrical therapy for CVD

Professor Bradley McConnell, a researcher at the University of Houston College of Pharmacy reported an effective protocol for  cardiovascular disease (CVD) by reprogramming human heart cells into specialised cells that conduct electricity throughout the heart to enable rhythmic heartbeat and repair diseased hearts.

McConnell, published in iScience, is the first to demonstrate the process by examining an alternative and unexplored cell type in cardiac regeneration. The researchers studies cardiac Purkinje cells, specialised cells from the cardiac conduction system (CCS) responsible for electrical signals that enable the heart to contract and relax synchronously.  

Currently, there are no treatments for cardiac cell death, which is the underlying basis of CVD.

By 2035, CVD prevalence is expected to increase to 45.1 percent (more than 130 million people) in the US, while the financial cost is projected to increase by more than $131 million over the next two decades, reaching an astounding $1.1 trillion. 

The research indicated that it may restore the efficiency of electrical signal conduction, resulting in improvements in cardiac function. 

“We are the first to demonstrate the successful direct reprogramming of human cardiomyocyte cell lines (AC16-CMs and iPSC-CMs) into Purkinje-like cells using a unique cocktail of small molecules,” reported both McConnell and Nicole Prodan, a doctoral student while in the McConnel lab.

“Direct reprogramming is a technique that produces an epigenetically unstable ‘plastic’ state on the cells to facilitate the conversion of a fully differentiated and matured cell into a different new cell type.” 

While several pharmacological treatments are currently available for heart failure, they do not prevent, cure or improve myocardial cell death and fibrotic scar formation, which are the main contributors to provoking heart failure.  

“The only cure is a heart transplant, which is unfortunately scarce,” said McConnell.   

Cell therapy for cardiac regeneration has been proposed as an alternative treatment to pharmacological agents. Unfortunately, the focus has been placed on replacing cardiac muscle cells (myocytes) in injured hearts, which has not been enough to ameliorate symptoms or cure the problem. 

“This is because often the cardiac myocytes implanted cannot be electrically activated in synchrony by the recipient’s heart and will contract at a different pace from the rest of the heart, inducing arrhythmias,” commented McConnell.   

“Our small molecule treatment of human cardiomyocytes leads to Purkinje differentiation resulting in key Purkinje cell gene expression and conduction of fast electrical signals; comparable to native Purkinje cells,” added Prodan. 

The study may not only help to advance the quest to find an optimised cell therapy for heart regeneration; but it brings the potential to be used for the development and investigation of new pharmacological therapies for heart diseases.