Natural Heart Regeneration

By Amanda Chase, PhD

February 20, 2020

Ischemic heart disease affects over 150 million people worldwide, and accounts for 10 million deaths globally per year, making it one of the greatest threats to human health in most western countries. Ischemic heart disease is when the blood flow, and therefore oxygen, is restricted or reduced in the heart muscle. This is caused by the narrowing of heart arteries, usually as the result of plaque buildup, which can ultimately lead to a heart attack, or myocardial infarction (MI). The lack of blood flow, or significant decrease, leads to damaged heart muscle. Current treatments include improving blood flow via medications or various procedures, including bypass surgery. Due to the enormity of people affected and the increasing cost associated with treating more patients, there are new pharmacologic therapies and strategies being developed. Despite these efforts, many patients are still progressing to heart failure despite optimal treatments for MI. Therefore, there is a significant and critical need for the development of novel therapeutic strategies to prevent and treat ischemic heart failure after myocardial infarction.

Recent efforts have been focused on heart regeneration. Following a heart attack, heart cells (cardiomyocytes) die, leading to heart muscle damage, and the non-viable cardiomyocytes are replaced with collagen scar. This ultimately leads to poor heart muscle contractility, and eventually leads to ischemic heart failure. Amphibians, such as newts, are able to undergo natural heart regeneration that results in minimal or no scar formation, in direct contrast to what is seen for humans. Recent work has suggested that this amazing ability of natural regeneration could be a neonatal phenotype, not just in amphibians. The implications of this has immense therapeutic potential for adult humans. However, current understanding of the mechanics of heart regeneration are severely limited by the scarcity of mammalian neonatal models of heart attack. Researchers at Stanford, led by Hanjay Wang, MD, and senior author Joseph Woo, MD, Professor of Cardiothoracic Surgery at Stanford, aimed to address this need by developing a neonatal rat myocardial infarction (MI; heart attack) model. Their work, recently published in Cells, introduces a neonatal rat model of MI that is capable of natural heart regeneration that results in minimal scar formation. This model is important for several reasons, namely that it further demonstrates neonatal heart regeneration and provides a more high-throughput model for developing a regeneration-based solution for treating ischemic heart disease following heart attack. A therapeutic for ischemic heart disease that allows heart muscle cell regeneration without scar formation would have the potential to save millions of lives every year.

Drs. Wang and Woo are both associated with the Stanford Cardiovascular Institute. Other authors from the Stanford Cardiovascular Institute include Michael Paulsen, and Yuanjia Zhu. Other Stanford authors include Camille Hironaka, Hye Sook Shin, Justin Farry, Akshara Thakore, Jinsuh Jung, Haley Lucian, Anahita Eskandari, Shreya Anilkumar, Matthew Wu, Mariana Cabatu, Amanda Steele, and Lyndsay Stapleton.

Hanjay Wang, MD

Joseph Woo, MD