Tension makes the heart grow stronger

September 25, 2017, Duke University
Epicardium cells covering the heart regenerate in a wave led by large cells that contain multiple nuclei per cell (magenta). These cells are under more mechanical tension (aqua streaks) than trailing cells which divide to produce cells with one nucleus each. Credit: Jingli Cao, Duke

By taking videos of a tiny beating zebrafish heart as it reconstructs its covering in a petri dish, scientists have captured unexpected dynamics of cells involved in tissue regeneration. They found that the depleted heart tissue regenerates itself in a wave, led by a front of fast-moving, supersized cells and trailed by smaller cells that multiply to produce others.

The nature of this wavefront—and the success of the that follows—is determined by mechanical tension that acts upon the . The results, published September 25 in the journal Developmental Cell, indicate a new paradigm for how forces acting in tissues can direct the decisions that cells make to regenerate lost tissues.

"Our findings open avenues for the study of cell cycle dynamics in regenerating tissue," said Jingli Cao, PhD, lead study author and a postdoctoral fellow in Ken Poss's lab at Duke University School of Medicine. "By manipulating the mechanical tension of cells, we also might be able to develop new bioengineering or translational approaches."

While the human heart can't fully heal itself after a heart attack, the zebrafish heart can easily replace cells lost to damage or disease. Scientists have spent many years probing the regenerative powers of this small striped fish in the hopes of uncovering clues that could improve therapy for human heart disease.

In 2015, Cao showed that he could remove the hearts from zebrafish and grow them in dishes in the laboratory, where the tiny two-chambered organs continued to beat and behave as if they were still tucked inside the animal. In this study, Cao and his colleagues exploited this system to monitor the regeneration of the epicardium, a thin layer of cells that cover the heart's surface.

The researchers destroyed most of the heart's epicardial layer, and then put the "explanted" organs under the microscope to capture the regeneration in action. They expected to see a population of cells that had rapidly replicated their DNA content and divided into new cells replenish the surface of the organ. While these cells definitely played a part, they were not leading the charge. Instead, regeneration was led by cells that replicated their DNA without dividing, effectively creating supersized cells with two times the cell machinery or more.

"Imagine you have a wound on your skin and you want to cover it as soon as possible, but you don't have enough cells," said Cao. "By making cells become larger, you could efficiently cover the wound. We think this tactic could increase the regenerative capacity of this population by covering the surface in an efficient manner."

The researchers measured a number of properties of the cells in the regenerative wavefront. They found that the bigger leader cells migrated across the surface of the heart at higher speeds than the smaller follower cells. When they measured the levels of tension experienced by the cells, they found that leader cells recoiled faster than follower cells when tiny incisions were applied, much like the surface of an inflated balloon retracts after bursting. Poss said that seems to keep the cells from dividing after DNA replication.

"This study is trying to understand the basic decisions cells make when they regenerate," said Poss, professor of cell biology at Duke University School of Medicine and director of the Regeneration Next Initiative at Duke. "If there are methods we could use to guide their decisions, to determine whether they generate larger cells or more cells through division, it could be one way to influence the ability of a tissue to repair."

The researchers plan to use their zebrafish heart explant culture system to screen for small molecules that could potentially increase the regenerative capacity of heart tissues. Such chemicals could one day form the basis for new drugs to repair the damage caused by a attack or other cardiovascular diseases.

Explore further: Study uncovers foundations of heart regeneration

More information: "Tension Creates an Endoreplication Wavefront That Leads Regeneration of Epicardial Tissue," Jingli Cao, Jinhu Wang, Christopher P. Jackman, Amanda H. Cox, Michael A. Trembley, Joseph J. Balowski, Ben D. Cox, Alessandro De Simone, Amy L. Dickson, Stefano Di Talia, Eric M. Small, Daniel P. Kiehart, Nenad Bursac, and Kenneth D. Poss. Developmental Cell, September 25, 2017. DOI: 10.1016/j.devcel.2017.08.024

Related Stories

Study uncovers foundations of heart regeneration

May 4, 2015
While the human heart can't heal itself, the zebrafish heart can easily replace cells lost by damage or disease. Now, researchers have discovered properties of a mysterious outer layer of the heart known as the epicardium ...

Stem Cell discovery refreshes the heart

August 7, 2017
Some people are better than others at recovering from a wounded heart, according to a new USC Stem Cell study published in Nature Genetics.

New molecule may hold the key to triggering the regeneration and repair of damaged heart cells

August 21, 2017
New research has discovered a potential means to trigger damaged heart cells to self-heal. The discovery could lead to groundbreaking forms of treatment for heart diseases. For the first time, researchers have identified ...

Scientists create 'beating' human heart muscle for cardiac research

March 17, 2017
Scientists at The University of Queensland have taken a significant step forward in cardiac disease research by creating a functional 'beating' human heart muscle from stem cells.

Recommended for you

New guidelines mean 1 in 3 adults may need blood pressure meds

May 23, 2018
(HealthDay)—One out of every three U.S. adults has high blood pressure that should be treated with medication, under guidelines recently adopted by the two leading heart health associations.

Surgery involving ultrasound energy found to treat high blood pressure

May 23, 2018
An operation that targets the nerves connected to the kidney has been found to significantly reduce blood pressure in patients with hypertension, according to the results of a clinical trial led in the UK by Queen Mary University ...

To have or not to have... your left atrial appendage closed

May 22, 2018
Each year in the U.S., more than 300,000 people have heart surgery. To reduce risk of stroke for their patients, surgeons often will close the left atrial appendage, which is a small sac in the left side of the heart where ...

Natural antioxidant bilirubin may improve cardiovascular health

May 18, 2018
Bilirubin, a yellow-orange pigment, is formed after the breakdown of red blood cells and is eliminated by the liver. It's not only a sign of a bruise, it may provide cardiovascular benefits, according to a large-scale epidemiology ...

New algorithm more accurately predicts life expectancy after heart failure

May 17, 2018
A new algorithm developed by UCLA researchers more accurately predicts which people will survive heart failure, and for how long, whether or not they receive a heart transplant. The algorithm would allow doctors to make more ...

New genes found that determine how the heart responds to exercise

May 17, 2018
A new study by researchers at Queen Mary University of London and University College London (UCL) has discovered 30 new gene locations that determine how the heart responds to and recovers from exercise.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.