In breakthrough study damaged mouse hearts regenerated by transforming scar tissue into beating heart muscle

April 18, 2012

Scientists at the Gladstone Institutes today are announcing a research breakthrough in mice that one day may help doctors restore hearts damaged by heart attacks—by converting scar-forming cardiac cells into beating heart muscle.

These scientists previously transformed such into cardiac muscle-like cells in petri dishes. But Gladstone postdoctoral scholar Li Qian, PhD, along with researchers in the laboratory of Deepak Srivastava, MD, has now accomplished this transformation in living animals—and with even greater success. The results, which may have broad human-health implications, are described in the latest issue of Nature, available online today.

Cardiovascular disease is the world's leading cause of death. Annually in the United States alone, the nearly 1 million Americans who survive a are left with failing hearts that can no longer beat at full capacity.

"The damage from a attack is typically permanent because heart-muscle cells—deprived of oxygen during the attack—die and scar tissue forms," said Dr. Srivastava, who directs cardiovascular and stem cell research at Gladstone, an independent and nonprofit biomedical-research institution. "But our experiments in mice are a proof of concept that we can reprogram non-beating cells directly into fully functional, cells—offering an innovative and less invasive way to restore heart function after a heart attack."

In laboratory experiments with that had experienced a heart attack, Drs. Qian and Srivastava delivered three genes that normally guide embryonic heart development—together known as GMT—directly into the damaged region. Within a month, non-beating cells that normally form transformed into beating heart-muscle cells. Within three months, the hearts were beating even stronger and pumping more blood.

"These findings could have a significant impact on heart-failure patients—whose damaged hearts make it difficult for them to engage in normal activities like walking up a flight of stairs," said Dr. Qian, who is also a California Institute for Regenerative Medicine postdoctoral scholar and a Roddenberry Fellow. "This research may result in a much-needed alternative to heart transplants—for which donors are extremely limited. And because we are reprogramming cells directly in the heart, we eliminate the need to surgically implant cells that were created in a petri dish."

"Our next goal is to replicate these experiments and test their safety in larger mammals, such as pigs, before considering clinical trials in humans," added Dr. Srivastava, who is also a professor at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "We hope that our research will lay the foundation for initiating cardiac repair soon after a heart attack—perhaps even when the patient arrives in the emergency room."

This research builds on the groundbreaking cell-reprogramming work of another Gladstone scientist and UCSF professor of anatomy, Shinya Yamanaka, MD, PhD. Dr. Yamanaka's 2007 discovery of a way to turn adult human skin cells into cells that act like embryonic stem cells has radically advanced the fields of cell biology and stem cell research. But these new Gladstone experiments go further by both completing the experiments directly in live hearts and by employing a technique called "direct reprogramming." Direct reprogramming could revolutionize the field of regenerative medicine, as it lets scientists transform one adult cell type into another without first having to revert back to the stem cell state. In the future, Gladstone scientists hope to use direct reprogramming not only to treat heart failure, but also for spinal cord injury and devastating illnesses such as Alzheimer's and Parkinson's disease.

Explore further: Gladstone scientist converts human skin cells into functional brain cells

More information: DOI: 10.1038/nature11044

Related Stories

Gladstone scientist converts human skin cells into functional brain cells

July 28, 2011
A scientist at the Gladstone Institutes has discovered a novel way to convert human skin cells into brain cells, advancing medicine and human health by offering new hope for regenerative medicine and personalized drug discovery ...

Helping the heart help itself: Research points to new use for stem cells

April 8, 2011
(PhysOrg.com) -- Human trials of stem cell therapy for post-heart attack patients have raised as many questions as they have answered -- because while the patients have tended to show some improvement in heart function, the ...

Transforming scar tissue into beating hearts: The next instalment

April 1, 2012
The latest research developments to reprogram scar tissue resulting from myocardial infarction (MI) into viable heart muscle cells, were presented at the Frontiers in CardioVascular Biology (FCVB) 2012 meeting, held 30 March ...

Recommended for you

Could aggressive blood pressure treatments lead to kidney damage?

July 18, 2017
Aggressive combination treatments for high blood pressure that are intended to protect the kidneys may actually be damaging the organs, new research from the University of Virginia School of Medicine suggests.

Quantifying effectiveness of treatment for irregular heartbeat

July 17, 2017
In a small proof-of-concept study, researchers at Johns Hopkins report a complex mathematical method to measure electrical communications within the heart can successfully predict the effectiveness of catheter ablation, the ...

Concerns over side effects of statins stopping stroke survivors taking medication

July 17, 2017
Negative media coverage of the side effects associated with taking statins, and patients' own experiences of taking the drugs, are among the reasons cited by stroke survivors and their carers for stopping taking potentially ...

Study discovers anticoagulant drugs are being prescribed against safety advice

July 17, 2017
A study by researchers at the University of Birmingham has shown that GPs are prescribing anticoagulants to patients with an irregular heartbeat against official safety advice.

Protein may protect against heart attack

July 14, 2017
DDK3 could be used as a new therapy to stop the build-up of fatty material inside the arteries

Heart study finds faulty link between biomarkers and clinical outcomes

July 14, 2017
Surrogate endpoints (biomarkers), which are routinely used in clinical research to test new drugs, should not be trusted as the ultimate measure to approve new health interventions in cardiovascular medicine, according to ...

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.