Injectable gel helps heart muscle revive after heart attack

Injectable gel that helps heart muscle revive after heart attack

11:36 AM, 4th December 2017
Injectable gel that helps heart muscle revive after heart attack
Cardiomyocytes, green, proliferating in a mouse heart after gel injection.

PHILADELPHIA, US: In mammals, including humans, the cells that contract the heart muscle and enable it to beat do not regenerate after injury. After a heart attack, there is a dramatic loss of these heart muscle cells and those that survive cannot effectively replicate. With fewer of these contractile cells, known as cardiomyocytes, the heart pumps less blood with each beat, leading to the increased mortality associated with heart disease.

Now, researchers at the University of Pennsylvania have used mouse models to demonstrate a new approach to restart replication in existing cardiomyocytes: an injectable gel that slowly releases short gene sequences known as microRNAs into the heart muscle.

Though the reasons cardiomyocytes don’t regenerate aren’t fully understood, the researchers used microRNAs that target signalling pathways related to cell proliferation and were able to inhibit some of the inherent “stop” signals that keep cardiomyocytes from replicating. This resulted in cardiomyocytes reactivating their proliferative potential.

With more heart cells dividing and reproducing, mice treated with this gel after heart attack showed improved recovery in key clinically relevant categories.   

The study was led by Edward Morrisey, professor in medicine; Jason Burdick, professor in Bioengineering in Penn Engineering; Leo Wang, a graduate student in Burdick’s lab; and Ying Liu, a postdoctoral researcher in Morrisey’s lab.   

It was published in the journal Nature Biomedical Engineering.

MicroRNA-based therapies have been studied in the past, but delivering the right dose to the right place has been a consistent challenge.

“Biologic drugs turn over very fast,” Morrisey said. “The microRNAs that we used last less than eight hours in the bloodstream, so having a high local concentration has strong advantages.”

The Morissey lab studies signalling pathways involved in heart and lung development and regeneration, while the Burdick lab has experience in designing biocompatible materials for drug delivery. The two groups collaborated to find the best way to get the microRNAs to the cardiomyocytes and have them persist long enough to be effective.   

To test their gel, the researchers used three types of mouse models.

The first group was normal, healthy mice. Within a few days after injecting the gel, their heart tissue showed increased biomarkers of cardiomyocyte proliferation.

The second group was “Confetti mice,” so called because they are genetically engineered such that they have individual cardiomyocytes that randomly express one of four different fluorescent proteins. These fluorescent labels allowed the researchers to see that individual cardiomyocyte were indeed dividing in response to the microRNA- gel treatment. After inducing heart attacks in the mice and introducing the microRNA-gel, the researchers could see that single red, yellow or green cardiomyocytes had become clusters, ranging from two to eight cells of the same colour.

The third group was mice in which heart attacks were also induced so that clinically relevant outcomes of the treatment could be studied. These mice showed improved recovery as compared to controls, including higher ejection fraction — more blood pumped with each beat — and smaller increases in heart size. Enlarged hearts are a common consequence of heart attacks, with the expanded area composed of non-contractile scar tissue.    

With promising results in mice, next steps for the researchers will involve testing human heart cells in vitro and conducting physiological experiments in animals with more human-like hearts, such as pigs.

More than a potentially life-prolonging treatment itself, the researchers see this microRNA-gel approach as representing a new, more direct avenue for precision regenerative medicine.   

“We’re seeing a change in approaches for regenerative medicine, using alternatives to stem cell delivery,” Burdick said. “Here, instead of introducing new cells that can have their own delivery challenges, we’re simply turning on repair mechanisms in cells that survive injury in the heart and other tissues.”

This work was funded by American Heart Association through an established investigator award to Burdick and a predoctoral fellowship to Wang, and the National Institutes of Health.

Jennifer J. Chung, Tao Wang, Ann C Gaffey, Minmin Lu, Christina A Cavanaugh, Su Zhou, Rahul Kanade and Pavan Atluri, all of the Penn Medicine, also contributed to the study.

Provisional patents concerning the technology described in this work have been filed.

© University of Pennsylvania

0 Comments

Login

Your Comments (Up to 2000 characters)
Please respect our community and the integrity of its participants. WOC reserves the right to moderate and approve your comment.

Related News


Total to supply LNG fuel for CMA CGM's new build ships

PARIS, FRANCE: Total SA and CMA CGM, a French container transportation and shipping company have signed an agreement covering the supply of around 300 ...

Read more
Orica plans new urea ammonium nitrate plant in Australia

MELBOURNE, AUSTRALIA: Orica has launched its new fertiliser business with plans for a local manufacturing plant for urea ammonium nitrate (UAN) in Mor ...

Read more
Dow completes selling part of corn hybrid seed business to CITIC

MIDLAND, US: The Dow Chemical Company, a subsidiary of DowDuPont (DWDP) has successfully completed the sale of a select portion of its Dow AgroScience ...

Read more
Denka to increase prices for polyvinyl alcohol globally

TOKYO, JAPAN: Denka Company Limited said that it will globally increase its sales price for polyvinyl alcohol (PVA), which is offered under the brand ...

Read more
Sumitomo to expand high-purity chemicals capacity in China

TOKYO, JAPAN: Sumitomo Chemical has decided to expand its production capacity for high-purity chemicals for semiconductors at Sumika Electronic Materi ...

Read more
TechnipFMC bags $4.2 bn refinery expansion contract in Bahrain

LONDON, UK/ PARIS, FRANCE/ HOUSTON, US: TechnipFMC (FTI) said that jointly with Samsung Engineering and Tecnicas Reunidas, it has been awarded a $4.2 ...

Read more