Reindeer paved the way for regenerative medicine

femaleAs Christmas approaches, reindeer stamp their hooves on fallen leaves and rush through white, snowy landscapes and folklore. This majestic creature with its spiny headdress plays a bigger role in the legend than simply serving as Santa’s personal chauffeur. They are also important models for studying biological superpowers.

Reindeer, along with their deer family cousins ​​the Cervidae, are capable of shedding and regenerating entire organs. both male and female reindeer Antlers can regrow, unlike other deer species where this phenomenon occurs only in male animals. deer lose one’s horn And let them grow back all at once. unprecedented speed Over the next few weeks.^1,2 At this stage, a special skin called velvet covers the antlers, which peels off after a few weeks, leaving only the bony antlers. The animals drop these structures again after a few months and begin regenerating new horns. Despite repeated molting and regeneration, deer perfectly regrow their antler skin with each cycle without leaving any scars.

when Li Chun YiAn antler biologist at Changchun University of Science and Technology, he started studying deer 40 years ago. He was impressed by the deer’s ability to shed and regenerate antlers and immediately realized the application of studying this process. “I started thinking about working in the field. And in the future, we may be able to help people regrow amputated limbs, legs or arms,” Li said.

Although regenerating amputated limbs is still a distant dream, Li and researchers have gained important insights into organ regeneration by studying the cellular and molecular processes behind tissue regeneration and repair in deer. These insights could lay the foundation for better wound and tissue repair treatments and pave the way for advancing the field of regenerative medicine.

Deer as a model to study regeneration

Deer are not the only mammals with regenerative abilities. skin injury In spiny mice, it heals without leaving a scar.³ The holes in the spiny rat’s ears are completely closed due to the newly formed blood vessels, cartilage, muscles and nerve fibers. But these rodents cannot regenerate entire organs, Li said. “Antler is the only mammalian organ that can completely regrow once it is lost.”

This is even more surprising considering that horns are complex organs. Jeff WiernaskiRegenerative biologist at the University of Calgary. “The organ is made up of nerves, a large blood supply, bone, and cartilage.”

Deer are also a valuable platform to study wound healing. “Deer are similar to humans in that their skin is tied to fascial muscles. They are also really fascinating because they are the only large animals that can move. [regenerate tissue].”

In addition to this, reindeer exhibit both. Regeneration and non-regeneration Healing type; While deer antler velvet heals without creating scars, cuts on the back skin do.⁴ Reindeer mimic human scars more closely than animals such as mice and rats that are commonly used to study scars. “So not only is it a great model for regeneration, it’s also a very good model for scar formation,” Biernaskie said.

The scientists hypothesized that studying these unique characteristics of the deer family could point the way to biological mechanisms that could enable regenerative healing in other animals. To harness the biology behind regeneration for medical applications, researchers must first understand which cells are involved in the process.

Stem cells help regenerate horns.

In the early 2000s, Li and his team focused on identifying different types of cells in horns. they used microscopy How to accurately determine your population cell Present in horns during regeneration.^5,6

When the research team deleted these cells in some deer, the animals showed no signs of antler regeneration throughout the season. The team transplanted these cell populations elsewhere on the bodies of some deer and observed the growth of antlers there. Important for horn regeneration.⁷

Li and the team focused on characterizing this cell population. Using several cellular and molecular techniques, the team identified these cells as: horn stem cells (ASC).⁸ Li’s team recently performed RNA sequencing of regenerating horns to assess the origins of these ASCs.¹ They identified a population of progenitor cells that give rise to ASCs. These progenitor cells can differentiate into bone cells and chondrocytes, which are important components of the horn.

To understand the mechanisms of ASC-induced regeneration, researchers studied the factors secreted by these cells. they observed it exosome— ASC-derived membrane-enclosed structures — prolonged proliferation of human bone marrow stem cells in culture.⁹ These findings indicate that exosomes derived from these cells could be used to develop treatments that promote regenerative healing.

Biernskie believes deer are worth studying for more than just whole organ regeneration. He and his team investigated reindeer’s ability to exhibit both skin regeneration and scarring to understand the biological differences underlying the two types of healing.⁴ Using RNA sequencing and proteomics, the research team discovered that wounds on velvet skin, which heal without scars, induce the activation of immune cells differently from skin wounds that form scars. Wounds on mouse skin that normally leave scars healed without scarring when researchers mimicked the signaling pathways activated in deer antler wounds. These results highlight that insights gained from the deer model can potentially be applied to regenerative healing in other mammals.

Next, the team will use a pig model to study which of the candidate pathways identified in reindeer can be applied across species. “If they work for the rat, they will work for the pig, [it is] It is very likely that it will work in humans as well,” Biernskie said.

The future of deer models: hit or miss?

Deer may provide important clues about regenerative processes in mammals, but deer are not widely studied. Both Li and Biernskie attributed this to logistical difficulties. Handling deer requires experts in large animal veterinary and wildlife medicine. Studying deer also requires facilities capable of handling such large animals. This makes it very expensive, Li said.

The model also has biological limitations that make it unsuitable for transgenic experiments that are easy to perform in mice or other common laboratory animals, Biernaskie said. To avoid these complications, researchers must first identify candidate regeneration-related genes in reindeer and then manipulate these genes in mouse models to verify their effects.

Additionally, velvet skin only covers the antlers for about three months a year, limiting the time researchers have to study them. As a result, Biernskie and team spent considerable time studying the differences between reindeer velvet and back skin wound healing. “We worked on the project for almost 10 years before we published it,” Biernskie said.

Despite these obstacles, researchers believe deer are a useful model that can provide many insights. “We’re very open to collaborating with other groups who have questions we don’t have access to but would like to test on that system,” Bierkaskie said. “So we can start to really leverage this. [model] Reach your full potential.”

But he doesn’t believe deer will become a mainstream animal model among researchers around the world anytime soon, largely due to the logistical challenges of working with such large animals. In these cases, it may be helpful to study other regenerative animals, including planarians and axolotls. This, combined with deer research, could provide important information about the different strategies that enable tissue regeneration in the animal kingdom. “We will start to piece this together over the next 10 years and new treatments will start to emerge.”