Stories about: heart regeneration

Can we teach heart cells to grow up?

normal and mutant cardiomyocytes
A mutant heart muscle cell (in green) surrounded by normal cells. The mutant cell lacks Srf, a master maturation gene. It is unable to grow in size and lacks the fine membrane invaginations that help coordinate muscle contractions (appearing as vertical striations in the normal cells). (IMAGE: GUO Y; ET AL. NAT COMMS 9 #3837 (2018).]

Scientists around the world have been trying to replace damaged heart tissue using lab-made heart-muscle cells, either injecting them into the heart or applying patches laced with the cells. But results to date have been underwhelming.

“If you make cardiomyocytes in a dish from pluripotent stem cells, they will engraft in the heart and form muscle,” says William Pu, MD, director of Basic and Translational Cardiovascular Research at Boston Children’s Hospital. “But the muscle doesn’t work very well because the myocytes are stuck in an immature stage.”

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Modified RNA offers drug-like approach to regenerating heart tissue

In mice, VEGF-A modRNA visibly improved blood supply to heart muscle (right image).
In mice, VEGF-A modRNA visibly improved blood supply to heart muscle (right image) as compared with no treatment.

Heart attacks cause the death of billions of the heart’s muscle cells. If these cardiomyocytes could be made to regenerate after an infarct, the heart could potentially be mended and its function restored.

Researchers have struggled to find the right approach to cardiac regeneration. Cell transplants have been tried, but the cells don’t engraft well long term and haven’t shown efficacy. Gene therapy to spur regeneration has been tested in animals, but dosage is hard to control and there’s a risk of genes going where they shouldn’t, causing tumors and other problems. Protein drugs have been tried, but they have short half-lives, being degraded or eliminated by the body before they can do much good. They are also hard to target to the heart.

A more recent approach to cardiac regeneration is to stimulate the body itself—and, specifically, progenitor cells— to repair the heart from within.

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Turning heart growth on and off: MicroRNAs could point to new treatments

In mice, boosting amounts of a microRNA family called miR-17-92 led to dramatic enlargements of embryonic and postnatal hearts, with thicker ventricle walls.

 

Challenging accepted wisdom about the heart, Boston Children’s Hospital cardiologist Bernhard Kühn, MD, recently showed that infants, children and adolescents are capable of generating new heart muscle cells, or cardiomyocytes. That work raised the possibility that scientists could stimulate regeneration to repair injured hearts.

Now, we have a potential therapeutic target to accomplish this: a family of microRNAs called miR-17-92 that regulates cardiomyocyte proliferation. In Circulation Research earlier this month, a team led by Kühn’s research colleague Da-Zhi Wang, PhD, demonstrates its potential.

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