Reindeer pave the way for regenerative medicine

WAs Christmas approaches, reindeer plunge into white snowy landscapes and folklore, stomping their hooves on fallen leaves. These majestic spiny-headed creatures play a bigger role in legends than just serving as Santa’s personal chauffeur. They are also important models for studying biological superpowers.

Reindeer, like their cousins ​​in the deer family, can shed and regrow entire organs. both male and female reindeer Unlike other deer species, they have the ability to regrow their antlers, but this phenomenon is specific to male animals. deer lose one’s horns and regrow them unprecedented speed over the next few weeks.^1,2 During this stage, a special skin called velvet covers the horn, and after a few weeks it falls off, leaving behind a bony horn. The animal sheds these structures again after several months and begins a new round of horn regrowth. Deer molt and regrow, each cycle perfectly regenerating the skin on their antlers without leaving any scars.

when Lee Chun-yiAn antler biologist at Changchun University of Science and Technology, he started studying deer 40 years ago. He was struck by the ability of deer to shed and regrow antlers, and soon realized the research applications of this process. “It made me want to work in the field, and in the future I might be able to help people regrow amputated limbs, legs and arms,” ​​Lee said.

Although regenerating amputated limbs is still a distant dream, Lee and his researchers have gained important insights into organ regeneration by studying the cellular and molecular processes behind tissue regeneration and repair in deer. Ta. These insights can lay the foundation for better wound and tissue repair therapies and pave the way to advance the field of regenerative medicine.

Deer as a model for studying regeneration

The deer family is not the only mammal with the ability to regenerate. skin damage In spiny rats, it heals without leaving any scars.³ The hole drilled in the spiny mouse ear is completely closed by newly formed blood vessels, cartilage, muscle, and nerve fibers. However, these rodents cannot regenerate entire organs, Lee said. “Horns are the only mammalian organs that can completely regenerate once lost.”

This is all the more remarkable considering that antlers are complex organs. Jeff Bianaskia regenerative biologist at the University of Calgary. “The organ is made up of nerves, a large blood supply, bones, and cartilage.”

Deer are also a valuable platform for studying wound healing. “Deer are similar to humans in that their skin is sort of connected to the underlying fascial muscles. They are also the only large animals that have [regenerate tissue]”

In addition to this, reindeer exhibits both Regenerative and non-regenerative types Types of healing. Velvet horns heal without scarring, but wounds to the skin on the back will leave scars.⁴ Reindeer more closely mimic human scars compared to animals such as mice and rats commonly used for scar research. “So this is not only a good model for regeneration, but also a very good model for scar formation,” Bielnaski said.

Scientists hypothesize that studying these unique characteristics of the cervid family may point the way to biological mechanisms that can stimulate regenerative healing in other animals. Masu. To harness the biology behind regeneration for medical applications, researchers first need to understand which cells are involved in the process.

Stem cells help horn regeneration

In the early 2000s, Lee and his team focused on identifying the different types of cells in the horn. they used microscopy How to accurately identify a population of cell Present in the corner when playing.^5,6

When the researchers removed these cells from several deer, the deer showed no signs of antler regrowth over the course of the season. The research team transplanted this cell population to other parts of the body of several deer and observed antler growth there, and found that these cells Important for horn regeneration.⁷

Li and his team then focused on characterizing this cell population. The research team used several cellular and molecular techniques to identify these cells as follows: antler stem cells (ASC).⁸ Li’s team recently performed RNA sequencing of regenerating horns to assess the origin of these ASCs.¹ They identified a population of progenitor cells that give rise to ASCs. These progenitor cells can differentiate into both osteocytes and chondrocytes, which are important components of the horn.

To understand the mechanisms behind ASC-induced regeneration, researchers studied factors secreted by these cells. they observed that exosomeASC-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 therapies that promote regenerative healing.

Biernaskie believes deer are worth studying beyond 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 found that velvet skin wounds, which show scarless healing compared to back skin wounds that form scars, lead to activation of different immune cells. I discovered it. Wounds in the mouse skin that normally scar healed without scarring when the researchers mimicked the signaling pathways active in antler velvet wounds. These results highlight that insights gained from the deer model may be applicable to regenerative healing in other mammals.

Next, the research team plans to use the pig model to study which of the candidate pathways identified from reindeer may hold true across species. “Because if they work on mice, they work on pigs. [it is] It’s very likely that it will work in humans as well,” Bielnaski said.

The future of deer models: hit or miss?

Although deer can provide important clues about mammalian regeneration processes, they have not been widely studied. Both Lee and Biernaski believe this is due to logistical difficulties. Handling deer requires experts in large animal veterinary medicine and wildlife medicine. Studying deer also requires facilities built to handle such large animals. That makes it very expensive, Lee said.

The model also has biological limitations, Bielnaski said, making it unsuitable for transgenic experiments, which are easier to do in mice and other common lab animals. To circumvent this complexity, researchers must first identify candidate regeneration-related genes in reindeer and then manipulate these genes in mouse models to test their effects.

Additionally, velvety skin only covers the horns for about three months of the year, so researchers have limited time to study them. As a result, Bielnaski and his team spent a great deal of time studying the differences in wound healing between reindeer velvet and back skin. “We worked on this project for almost 10 years before publishing it,” Biernaskie says.

Despite these obstacles, researchers believe deer are a useful model that can yield many insights. “We are very open to working with other groups that may not have access but have questions that they would like to test in their systems,” Biacaski said. “Then you can really start leveraging this. [model] Maximize its potential. ”

But he doesn’t think deer will soon join mainstream animal models among researchers around the world, mainly due to the logistical challenges of working with such large animals. In such cases, it may be helpful to study other regenerating animals, such as planarians and axolotls. Combining this with studies of deer provides important information about the different strategies that enable tissue regeneration in the animal kingdom. “Over the next 10 years we will really start to piece this together and new treatments will begin to emerge.”