The Great Divide: CIRM-Funded Research Resolves Controversy over the Regenerative Powers of Heart Cells

The human heart contains approximately 3 billion beating heart cells. But is this number predetermined from birth? Or do these cells have the ability to divide and replicate?

These questions have long dogged scientists—who initially thought that heart muscle cells, or cardiomyocytes, were incapable of dividing. But in recent years, new evidence came to light indicating that heart cells are, in fact, capable of regenerating. But how, or why, or even to what extent, remained a mystery.

Researchers employed a variety of techniques to try and answer this question—one group even tried carbon dating (a technique generally reserved for dating archaeological remains) to pinpoint the age of a human’s heart cells—but to no avail.

So the research team, led by Drs. Irving Weissman of Stanford University and Reza Ardehali, formerly of Stanford and now at UCLA, tried something new.

Published online recently in the Proceedings of the National Academy of Sciences, they developed a new genetics-based approach that could directly detect the moment that a heart cell divided. They called this technique the mosaic analysis with double markers, or MADAM.

Using the MADAM technique, the researchers observed in mouse models the timing and frequency by which heart cells grow and proliferate. In so doing, they found that—while rare after the first month of life—cardiomyocytes do divide within the heart in a symmetrical fashion. Specifically, the team measured a regeneration rate of just under one percent per year.

This research, which was supported by a CIRM Grant, are essential for any future clinical studies into heart regeneration, as they can now take into account the existing regenerative capabilities of the heart. As Dr. Ardehali explained in UCLA's news release:

“This is a very exciting discovery because we hope to use this knowledge to eventually be able to regenerate heart tissue. The goal is to identify the molecular pathways involved in symmetric division of cardiomyocytes and use them to induce regeneration to replenish heart muscle tissue after disease or injury.”

Anne Holden