Stem Cell discovery refreshes the heart

August 7, 2017
Heart muscle cells (red) with nuclei (blue). On the far right is a regenerative cell, which only has one nucleus, called a mononuclear diploid cardiomyocyte. Credit: Michaela Patterson/USC

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

In the study, first author Michaela Patterson, a postdoctoral fellow in the laboratory of Henry Sucov, and her colleagues focused on a regenerative type of heart muscle cell called a mononuclear diploid cardiomyocyte (MNDCM). Zebrafish and newborn mammals, including mice and humans, have large numbers of MNDCMs and a relatively robust ability to regenerate heart muscle. However, adult mammals have few MNDCMs and a correspondingly limited capacity for regeneration after an injury such as a heart attack.

Even so, the situation for adult mammals is not uniformly dire: Patterson and her co-authors observed a surprising amount variation in the number of MNDCMs among different strains of adult mice. In some strains, MNDCMs accounted for only 1.9 percent of . In others, a full 10 percent were MNDCMs. As expected, the higher the percentage of MNDCMs, the better the mice fared in regenerating their heart muscle after injury.

"This was an exciting finding," said Patterson. "It suggests that not all individuals are destined to permanent heart loss after a , but rather some can naturally recover both mass and function. If we can identify the genes that make some individuals better at it than others, then perhaps we can stimulate regeneration across the board."

Using an approach called a genome-wide association study, the researchers indeed identified one of the key genes underlying this variation: Tnni3k. By blocking this gene in mice, the researchers produced higher percentages of MNDCMs and enhanced heart regeneration. In contrast, activating this gene in zebrafish decreased MNDCMs and impaired heart regeneration.

Sucov—senior author and professor of stem cell biology and regenerative medicine, integrative anatomical sciences, and biochemistry and molecular biology—described how this early discovery could be a first step towards a preventive strategy to mitigate heart disease, the leading cause of death in the Western world.

"The activity of this gene, Tnni3k, can be modulated by small molecules, which could be developed into prescription drugs in the future," he said. "These small molecules could change the composition of the heart over time to contain more of these regenerative . This could improve the potential for regeneration in adult hearts, as a preventative strategy for those who may be at risk for heart failure."

Explore further: Scientists create 'beating' human heart muscle for cardiac research

More information: Michaela Patterson et al, Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration, Nature Genetics (2017). DOI: 10.1038/ng.3929

Related Stories

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.

Cancer drug could promote regeneration of heart tissue

February 3, 2017
An anticancer agent in development promotes regeneration of damaged heart muscle 0- an unexpected research finding that may help prevent congestive heart failure in the future.

Mammalian heart regenerative capacity depends on severity of injury

January 22, 2015
A new study by researchers at Children's Hospital Los Angeles has shown that neonatal mouse hearts have varying regenerative capacities depending upon the severity of injury. Using cryoinjury - damaging the heart through ...

The heart's own stem cells play their part in regeneration

November 29, 2013
(Medical Xpress)—Up until a few years ago, the common school of thought held that the mammalian heart had very little regenerative capacity. However, scientists now know that heart muscle cells constantly regenerate, albeit ...

Low-oxygen environment leads to heart regeneration in mice, research shows

October 31, 2016
Normal, healthy heart muscle is well-supplied with oxygen-rich blood. But UT Southwestern Medical Center cardiologists have been able to regenerate heart muscle by placing mice in an extremely low-oxygen environment.

Recommended for you

How genes and environment interact to raise risk of congenital heart defects

October 19, 2017
Infants of mothers with diabetes have a three- to five-fold increased risk of congenital heart defects. Such developmental defects are likely caused by a combination of genetic and environmental factors. However, the molecular ...

Mouse studies shed light on how protein controls heart failure

October 18, 2017
A new study on two specially bred strains of mice has illuminated how abnormal addition of the chemical phosphate to a specific heart muscle protein may sabotage the way the protein behaves in a cell, and may damage the way ...

Newborns with trisomy 13 or 18 benefit from heart surgery, study finds

October 18, 2017
Heart surgery significantly decreases in-hospital mortality among infants with either of two genetic disorders that cause severe physical and intellectual disabilities, according to a new study by a researcher at the Stanford ...

Saving hearts after heart attacks: Overexpression of a gene enhances repair of dead muscle

October 17, 2017
University of Alabama at Birmingham biomedical engineers report a significant advance in efforts to repair a damaged heart after a heart attack, using grafted heart-muscle cells to create a repair patch. The key was overexpressing ...

Physically active white men at high risk for plaque buildup in arteries

October 17, 2017
White men who exercise at high levels are 86 percent more likely than people who exercise at low levels to experience a buildup of plaque in the heart arteries by middle age, a new study suggests.

High blood pressure linked to common heart valve disorder

October 17, 2017
For the first time, a strong link has been established between high blood pressure and the most common heart valve disorder in high-income countries, by new research from The George Institute for Global Health at the University ...

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.