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New directions in heart and brain regenerative research

Why are some tissues and organisms able to regenerate while others can­not? It is a fundamental question that drives discovery in the Vickaryous lab at the University of Guelph’s Ontario Veterinary College. 

Gecko cardiac muscle cellsUsing a species of lizard — the leopard gecko — as a model to explore naturally occurring tissue replacement, Biomedical Sciences professor Matt Vickaryous focuses on the biology of regeneration and repair, research that may offer insight into wound healing in humans. Although long overlooked, lizards such as geckos are providing valuable new information about how reptiles, unlike humans, can regenerate lost or dam­aged tissues. 

Since joining OVC in 2008, Vickaryous has published numerous papers investigating tissue regrowth behaviour of geckos. This work includes a 2017 study that identified the type of stem cell that enables geckos to regrow the spinal cord in their tails. Additional research looks at the geckos’ ability to heal wounds to their skin without scarring. Findings in both areas may one day have impli­cations in human medicine.

Now, new research from graduate students Kathy Jacyniak and Rebecca McDonald has found evidence that geckos can also replace cells in their heart and brain, suggest­ing that their regenerative capabilities may extend to other organs. 

While most regenerative work has focused on zebrafish or sala­manders, less is known about other species. Lizards, such as the gecko, are more closely related to mammals than salamanders and thus might offer important clues for clinical medicine, McDonald says. 

In each of their studies, Jacyniak and McDonald found evidence that leopard geckos have the ability to routinely generate new, highly spe­cialized cells that are otherwise rarely regrown in mammals. 

“In most species, when cells are injured or die in the brain or the heart they are replaced with scar tissue, and this impacts function,” says Jacyniak. “Using naturally occurring examples of regeneration, such as the leopard gecko, we seek to understand how tissues and cells can be restored without scarring.” Jacyniak adds that further research in this area may have many translational benefits for other species, including our own.

For both Jacyniak and McDonald, their research focused on discovering what the animals do naturally, without any clinical intervention. 

“We found the geckos’ heart muscle cells (cardiomyocytes) continuously divide and create new cells,” says Jacyniak. To be certain the cells were actually dividing, she needed to use multiple methods and label the cells for various proteins.

Stem cells in the leopard gecko brain“I found that around 10 per cent of cardiomyocytes are dividing at any given time, whereas in mammals it is less than one per cent per year,” she notes. 

McDonald’s research looks at a region of the brain known as the medial cortex, an area that corre­sponds to the human hippocampus or memory centre. Using a chemical label that identifies dividing cells, McDonald was able to track when new cells appeared, where they migrated to and determine when they ultimately became new neurons in the brain. 

To their surprise, the team also found that cell proliferation in both the heart and brain was not slowed by tail loss or tail regeneration in the gecko, indicating that wound healing does not alter routine cell division elsewhere in the body.

With this initial research on brain and heart cells in place, research is now moving to the next step — analyzing how these cells respond to injury with a focus on both structure and function. 

Jacyniak has already begun this work as she pursues her PhD at OVC. Jacyniak first came to OVC for the one-year Master of Biomedical Sciences (MBS) program to get a taste of research life after she completed her undergraduate degree at the University of Toronto. “I tried it and I loved it, so I transferred into the two-year Master of Science (MSc) program,” shares Jacyniak. “There are so many things I want to answer. After doing all the ground work, I am excited to explore the next steps in this research as I enter my PhD.” McDonald is also continuing studies at OVC, albeit in a slightly different direction, as she pursues veterinary medicine, having joined the OVC DVM Class of 2022 in fall 2018. She takes along her passion for regenerative medicine and exotics, particularly the leopard gecko.

Photo of leopard geckoThe gecko goods

As with many types of lizards, leopard geckos can detach a portion of their tails, in a process known as tail autotomy, and regenerate a replacement tail. They can also regenerate skin on both their body and tail without forming a scar (unlike what happens in mammals, such as humans). 

Leopard geckos are members of the Eublepharidae, a group of related geckos known as ‘true eyelid’ geckos. Unlike other types of geckos, eublepharids have movable eyelids.

Geckos are native to Pakistan, India, Afghanistan, and possibly Iran.

They have temperature-dependent sex determination meaning the temperature the geckos are exposed to during embryonic development will help determine their sex.

The lowdown on lizards

Lizards come in a variety of shapes and sizes. Their adult body length ranges from about 1.6 cm to more than 300 cm in length and can vary in shape. Some lizards have four limbs and others are completely limbless.

Lizards are amniotes and are the closest relatives of mammals capable of appendage (tail) regeneration. The study of tail regeneration in lizards offers insight into the evolution of wound healing in mammals and may help explain why some fish, amphibians and lizards are better at healing wounds than mammals.

Lizards have the same number of species as mammals – approximately 6,500.

Originally published in the Winter/Spring 2019 Crest Magazine