Journal News

A second chance for a healthy heart

Researchers use cellular reprogramming to make damaged organ almost good as new
Marissa Locke Rottinghaus
April 19, 2023

A recent study using mice has revealed a way to turn back the clock after heart attack. The researchers behind the work used RNAs to instruct cells in an injured heart to eliminate scar tissue and re-create cardiac muscle, allowing the heart to function like new again.

Cardiovascular disease, including heart attack, is the leading cause of death worldwide.

Courtesy of Conrad Hodgkinson
Cardiac muscle cells derived from cardiac fibroblasts. Fibroblast marker Fsp1 (red), cardiac muscle cell marker troponin I (green) and nuclei (blue).
Courtesy of Conrad Hodgkinson
Fibroblasts were isolated from adult murine cardiac tissue. Transcription factor Epas1 (red), cytoskeleton (green) and nuclei (blue).

“Adult human hearts are not very good at repairing themselves,” said Conrad Hodgkinson, an associate professor of medicine and pathology at Duke University School of Medicine who oversaw the study. “Once they have a heart attack or any type of damage, there's no capacity to replace the heart muscle that dies. So, what the heart does to stop itself from basically blowing up is it activates fibroblasts to come in and form a scar.”

Like the scars on skin that result from injury or surgery, the scar tissue generated in the heart after a heart attack is tough and nonflexible and can prevent the organ from functioning at its full potential, Hodgkinson said.

Hodgkinson and his team wanted to find an efficient way to convert the scar tissue back into functioning cardiac muscle to essentially reverse the effects of a heart attack. To do this, they set out to find a way to transform fibroblasts, a type of cell that contributes to the formation of connective tissue, into heart muscle cells via a process called cellular reprogramming. Hodgkinson’s lab delivers reprogramming instructions to cells in form of RNAs. However, they found adult fibroblasts are not very good at following the instructions and are resistant to reprogramming.

Courtesy of Conrad Hodgkinson
Cardiac tissue sections two months after injury treated with control; miR combo plus a non-targeting control siRNA; or miR combo plus an Epas1 targeting siRNA cocktail.

An old adage states: Kids are resilient. However, there may be biology to back it up.

“We found that if you take cardiac fibroblasts from juveniles, they reprogram very nicely,” Hodgkinson said. “But, if you take cardiac fibroblasts from adults, they don't, in fact, respond at all. So, we tried to understand whether the aging process was actually interfering with fibroblast reprogramming.”

Hodgkinson and his team discovered that a protein oxygen sensor, Epas1, prevents adult fibroblasts from reprogramming themselves. The researchers were able to harness the regenerative capacity of young cells by blocking Epas1 in adult fibroblasts.

“When we reversed the fibroblast aging process, essentially making the fibroblasts think they were young again, we converted more fibroblasts into cardiac muscle,” Hodgkinson said.

The researchers formulated a cocktail of RNAs and packaged them into exosomes, a natural product produced by most cells. This technology allowed them to deliver the exosomes without surgical interventions. Exosome packages have unique properties that guide them to cardiac fibroblasts inside an injured heart.

“Exosomes are kind of like shopping bags,” Hodgkinson said. “The cell sticks a lot of stuff into a big fat ball to send out and signal to other cells. They are a way cells can talk to each other.”

When the researchers used the RNA-filled exosomes to instruct the fibroblasts to reprogram themselves in a mouse that had just experienced a heart attack, the results were, according to Hodgkinson, “impressive.”

“We were able to recover almost all of the cardiac function that was lost after a heart attack by reversing the aging of the fibroblasts in the heart,” Hodgkinson said. Their findings were published in the Journal of Biological Chemistry. 

Cellular reprogramming, coupled with reversing cellular aging, has limitless future applications, including restoring neuron loss in the brains of dementia patients and eliminating skin scarring in psoriasis patients without invasive surgical interventions, Hodgkinson said.

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition monthly.

Learn more
Marissa Locke Rottinghaus

Marissa Locke Rottinghaus is the Editorial Content Manager for ASBMB.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

AI-designed biomarker improves malaria diagnostics
Journal News

AI-designed biomarker improves malaria diagnostics

Oct. 8, 2025

Researchers from the University of Melbourne engineered Plasmodium vivax diagnostic protein with enhanced yield and stability while preserving antibody-binding, paving the way for more reliable malaria testing.

Matrix metalloproteinase inhibitor reduces cancer invasion
Journal News

Matrix metalloproteinase inhibitor reduces cancer invasion

Oct. 8, 2025

Scientists at the Mayo Clinic engineered a TIMP-1 protein variant that selectively inhibits MMP-9 and reduces invasion of triple-negative breast cancer cells, offering a promising tool for targeted cancer research.

Antibiotic sensor directly binds drug in resistant bacteria
Journal News

Antibiotic sensor directly binds drug in resistant bacteria

Oct. 8, 2025

Researchers at Drexel University uncover how the vancomycin-resistant bacterial sensor binds to the antibiotic, offering insights to guide inhibitor design that restores antibiotic effectiveness against hospital-acquired infections.

ApoA1 reduce atherosclerotic plaques via cell death pathway
Journal News

ApoA1 reduce atherosclerotic plaques via cell death pathway

Oct. 1, 2025

Researchers show that ApoA1, a key HDL protein, helps reduce plaque and necrotic core formation in atherosclerosis by modulating Bim-driven macrophage death. The findings reveal new insights into how ApoA1 protects against heart disease.

Omega-3 lowers inflammation, blood pressure in obese adults
Journal News

Omega-3 lowers inflammation, blood pressure in obese adults

Oct. 1, 2025

A randomized study shows omega-3 supplements reduce proinflammatory chemokines and lower blood pressure in obese adults, furthering the understanding of how to modulate cardiovascular disease risk.

AI unlocks the hidden grammar of gene regulation
Feature

AI unlocks the hidden grammar of gene regulation

Sept. 30, 2025

Using fruit flies and artificial intelligence, Julia Zeitlinger’s lab is decoding genome patterns — revealing how transcription factors and nucleosomes control gene expression, pushing biology toward faster, more precise discoveries.