Zebrafish Tissue Can Trigger Mammal Heart Regeneration

Credit: Uri Manor, NICHD

Injecting extracellular matrix taken from zebrafish hearts, which are famous able to regenerate, appears to initiate similar rejuvenation in mammalian heart tissue too

Zebrafish are rather unique in the natural world, in that they can fully regenerate their heart, even when up to 20% has been damaged. Scientists have therefore been scrambling to work out which genes and molecular signals are involved. Given that genes are remarkably conserved throughout the animal kingdom, there is a chance that similar signals could kickstart latent regenerative ability in mammals too (including humans). 

Enter the ECM (extracellular matrix)

Heart cells are surrounded in a matrix layer called the ECM. This provides structural support and contains abundant locked in proteins that when released tell the nearby cells to behave in a certain way. ECM is present across the entire body and plays an essential role in skin, as well as skin aging. Breaking down the ECM can even encourage cancer growth, as well as wound healing. 

Healing mammalian hearts 

A team of researchers decided to test ECM components extracted from zebrafish in mice and human cells, to see if it had any beneficial effect. They first froze zebrafish heart tissue - bursting the cells but leaving a remaining ECM. This prevented immune rejection and decellularized the extract. They then injected this ECM into damaged mouse hearts. 

"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. Because ECMs are composed of collagen, elastin, carbohydrates and signaling molecules and have no cell surface markers, DNA or RNA from the donor, the recipient is less likely to reject the treatment"

Mouse cardiac function was improved almost immediately, and healing was visible within 5 days post-treatment; increasing the heart beat strength in contrast to untreated animals. More importantly, ECM taken from zebrafish hearts that was in the process of healing was even more effective in aiding healing. While the concept hasn't been tested in detail on human tissue, the team did have time to observe the effects of ECM on human cardiac cells in the laboratory. Initial observations suggested that it protected the cells from stress but we will have to await further testing in coming research. 

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