A fishy solution to restoring the heart’s regenerative abilities

Our heart loses its ability to regenerate itself once we leave the womb, but can the zebrafish help us recover this lost function?(Credit: kazakovmaksim/Depositphotos)

The zebrafish may not look anything like us but scientists believe it holds the key to fighting heart disease, thanks to its remarkable ability to repair its own heart. In a novel study, a University of Pittsburgh researcher has found success in using the extracellular matrices (ECM) in zebrafish to jumpstart mammalian cardiac tissue regeneration, possibly bringing science closer to fixing a "broken heart."

Apart from sharing 70 percent of the same genes, the zebrafish's heart also shares many similarities with ours, except for a few notable differences, chief of which is its ability to heal itself when damaged. Indeed, destroy or remove up to 20 percent of a zebrafish's heart and within a month, it will be as good as new, having repaired itself completely. Human hearts are not so fortunate. Although we have this regenerative ability in the embryonic stage, we lose it rapidly after we are born. Why is this so and more importantly, can it be restored? This is the crux of bioengineering professor Yadong Wang's research: to see if ECM plays a role in the zebrafish's regenerative ability and whether it can coax a similar response in mammalian hearts.

While some researchers have sought to tap into the heart's own self-repair capabilities and use pluripotent stem cells to make functional heart tissue that can be worn as a 3D patch, this study focuses on the architectural foundation of organs – ECM. The importance of ECM lies in that it is involved in nearly all cellular activities, including tissue development and regeneration. In addition, using zebrafish ECM departs from conventional studies that focus on mammalian ECM as the latter is derived from a fibrosis-prone tissue that impedes recovery, states the study.

To put their hypothesis regarding the regenerative abilities of zebrafish ECM to the test, Wang and his team first separated them from the cells to ensure that the recipient mice hearts would not reject them.

"It's difficult to inject foreign cells into a body because the body will recognize them as foreign and reject them; that's not the case with ECM," said Wang, explaining that ECMs are less likely to be rejected as they are composed of collagen, elastin, carbohydrates and signalling molecules and have no cell surface markers, DNA or RNA from the donor.

They then injected the ECM into a mouse heart with damaged muscles. According to Wang, it restored heart function almost immediately and the healing effect was noticeable within five days after treatment. Within a week, it was beating more strongly than the untreated test subjects.

"The heart beats as if nothing has happened to it," said Wang. "And our approach is really simple."

To further test the effectiveness of zebrafish ECM, the team took samples from normal specimens as well as those with damaged hearts in which the ECM had already begun the healing process, and found that while both were effective in repairing damage, the latter was more potent in restoring heart function in the mice.

As part of the study, the researchers also simulated the harsh environment that develops when there is a heart attack or disease, and found that the zebrafish ECM protected in vitro human cardiac myocytes –specialized heart muscle cells – from the stresses.

Following this project, Wang hopes to expand heart treatments to larger mammals in a future study and is using this process to regenerate nerves in mammals.

The results of the study were published in Science Advances.

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