18 November

Spiny mouse as a model for heart repair after injury

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Adult mammals, including humans, cannot naturally repair heart tissue after an infarct. The contrary is the case: after an infarct, heart function usually worsens with time, a process known as pathological remodeling. Researchers from the group of Kerstin Bartscherer in collaboration with the group of Eva van Rooij and the Center for Cellular Nanoanalytics (Osnabrück University, Germany) have now found a mammal that is different. The spiny mouse repairs its heart much more efficiently after an infarct than common laboratory mice and avoids pathological remodeling. Ultimately, these results pave the way to identify new targets for therapies that promote heart repair in humans. The findings were published in npj Regenerative Medicine on 17 November.

The spiny mouse is a rodent species characterized by its stiff guard hairs, much like those of a hedgehog. Unlike most mammals, the spiny mouse is able to heal deep skin wounds without leaving a scar. That makes this animal a powerful model organism for regenerative medicine. In their current study, the group of Kerstin Bartscherer tackled the question whether this amazing regenerative capacity of spiny mice extends towards the heart, one of the hardest organs to repair.

Learn from regeneration

Tim Koopmans – first author on the new publication in npj Regenerative Medicine – explains: “Heart failure remains the leading cause of death worldwide, which can be attributed to the inability of the heart to regenerate after injury, for example due to a heart attack. Instead, we form a debilitating scar that, although crucial for survival, drives a cascade of harmful changes that may ultimately overwhelm the heart’s coping mechanisms. We can therefore learn a lot from animals that are able to regenerate adult cardiac tissue.”

Overview of the injured heart showing the presence of blood vessels in the spiny (Acomys), but not common laboratory mouse (Mus). Credit: Tim Koopmans, copyright: Hubrecht Institute.
Improved heart function

The researchers studied a group of spiny mice and a group of common laboratory mice. In both groups, they were able to model heart injury similar to how it occurs in humans. Although the acute response to the injury turned out to be comparable in both types of mice, the spiny mice showed a much higher survival rate and showed little to no signs of pathological remodeling (i.e., changes in the heart that affect its size, shape or function, typically associated with a worse prognosis in humans). This was accompanied by a partial recovery of heart function over time.

Correspondingly, spiny mice formed and maintained new blood vessels that were fully functional, changed the structural organization of the scar and (partially) restored the presence of some cell types. All of these results have likely contributed to the observed differences in heart function after injury.

Translation to humans

Model organisms for research into adult heart repair are rare and comprise mainly non-mammalian animals. However, the results from these models have been difficult to translate into successful therapies for humans due to differences in body physiology. “With the spiny mouse, we found a mammal that can naturally repair its heart and can therefore serve as a role model for humans. It is more compatible with human physiology and should make translation to human heart injury easier,” Koopmans and Bartscherer explain.

Although the spiny mouse cannot regenerate its heart in the same way it heals its skin, its response to heart injury presents numerous potential research avenues. “We need to dive deeper into the molecular mechanisms, so we can hopefully find targets for new medication. In the long-term, this may lead to therapies that promote heart repair in humans,” Koopmans concludes.

Publication

Ischemic tolerance and cardiac repair in the spiny mouse (Acomys). Tim Koopmans, Henriette van Beijnum, Elke F. Roovers, Antonio Tomasso, Divyanshu Malhotra, Jochem Boeter, Olympia E. Psathaki, Danielle Versteeg, Eva van Rooij, Kerstin Bartscherer. Npj Regenerative Medicine, 2021.

 

 

Kerstin Bartscherer is a group leader at the Hubrecht Institute.