Vet med scholars publish groundbreaking research on skin regeneration

Regenerative healing may be on the horizon for both animals and humans, say experts at the University of Calgary’s Faculty of Veterinary Medicine (UCVM). And reindeer might be the key.

A new study by UCVM researchers, led by Dr. Jeff Biernaskie, is looking at how reindeer can help us understand tissue regeneration better than ever before. 

“The basic question that my lab is interested in is why is it that mammals, including humans, have evolved to form scars after severe tissue injury. How can we alter that process in order to reinstate regeneration?” says Biernaskie, a professor of stem cell biology and regenerative medicine and the Calgary Firefighters Burn Treatment Society (CFBTS) Chair in Skin Regeneration and Wound Healing.

He is the lead author of “Fibroblast Inflammatory Priming Determines Regenerative Versus Fibrotic Skin Repair in Reindeer,” a study published in the leading scientific journal, Cell. The study was funded by a Natural Sciences and Engineering Research Council (NSERC) grant, as well as through philanthropy with support from the CFBTS.

Reindeer have a special ability to regenerate tissue

Biernaskie says that, while humans can regenerate skin perfectly as embryos, they lose that ability after birth, leading to scar tissue formation. He says the reason for this shift comes down to humans evolving to heal wounds faster to prevent infection, resulting in what Biernaskie calls, “a dysfunctional piece of skin.” Reindeer, however, maintain the ability to regenerate tissue well into adulthood, as seen in the annual growth of their antlers that are shed in winter and regrown over the summer. 

“If reindeer have identical wounds on the antler velvet and on the back skin, the velvet skin regenerates back to normal without scar, while the back skin forms a raised dysfunctional scar,” he says. “Our work takes advantage of cutting-edge single-cell genomics to show that this occurs because dermal cells in the back skin, called fibroblasts, provide signals to the immune system that intensifies their response to injury and biases the healing process to form scars (much like in adult humans). However, fibroblasts in the velvet decrease inflammation during wound healing and this allows for regeneration instead.”

The hunt for a more accurate 'blueprint'

For Biernaskie, being able to work with reindeer means gathering a more accurate “blueprint” of what is required to promote skin regeneration in humans, as reindeer size and physiology more closely represents that of humans compared to other animals that have been used to study regeneration like salamanders, which are able to regenerate their limbs or tail. He credits UCVM’s large-animal veterinary and wildlife expertise as key enablers of this unique research.

“There are few institutions, not just in Canada but around the world, that have the specialized veterinary expertise and state-of-the-art facilities to enable this kind of research,” he says. “We’re probably only one of two or three laboratories around the world that are able to work on antler regeneration as a model of tissue regeneration.” 

The study was co-led by Dr. Sarthak Sinha and Dr. Holly Sparks. Sparks, now an assistant professor of large animal surgery at UCVM and Canada Research Chair in Equine Regenerative Medicine, completed the work as part of her PhD studies in Biernaskie’s lab. Sinha also completed his PhD in the Biernaskie lab as an MD-PhD candidate and Vanier Scholar in the Leaders in Medicine program. The study also included collaborations with Yale University, University of Kentucky and Morgridge Institute for Research in Wisconsin.

New insights into tissue regeneration as we age

“Pioneering work in the 1970s first discovered that human fetal skin, unlike its adult counterpart, heals without scar,” explains Sinha. “Our work has also uncovered new insight into why mammals, including humans, lose our ability to regenerate tissues as we age. We saw that, when velvet skin was allowed to naturally age, it became progressively less regenerative, which coincided with fibroblasts adopting an inflammatory state. We call this ‘fibroblast inflammatory priming,’ and show that the presence of these signals is sufficient to suppress regeneration and drive scar formation.”

Sparks describes the project as “a fantastic example of interdisciplinary collaborative research at UCVM. We are fortune here to have many experts in wildlife health and significant resources focused on understanding and protecting the health, welfare and conservation of this magnificent species. Using this information, we can begin to develop new approaches to improve healing for both humans and animals.”

Biernaskie says the reindeer herd used in the study is also aiding UCVM in studying other One Health challenges such as the impact of climate change on sensitive species and conditions such as chronic wasting diseases.

While all three researchers agree humanity is far from the full-limb regeneration of comic book heroes and cartoon characters, this research is a stepping stone in the right direction towards scar-free healing. Further research on the topic of regeneration will continue at UCVM in the coming years.