Samantha Payne is a PhD student in the Chemical Engineering and Applied Chemistry department at the University of Toronto. She has previously investigated regeneration in a non-mammalian gecko model during an MSc program, and now currently combines stem cell biology and biomaterials to encapsulate and deliver therapeutic cells to the stroke-injured brain. Samantha became interested in scientific communication as a means to combine her love of writing and science to share exciting scientific topics and discoveries to a broader community.
With the holiday season upon us, it sometimes feels like everywhere we go we are bombarded with cheerful festive tunes, including the well known song about how Rudolph the Red Nosed Reindeer saved Christmas. Despite all the fuss around Rudolph’s bright red nose, there is another anatomical feature of Rudolph’s and ‘all of the other reindeer’ that is quite remarkable and deserves some recognition: every year, male deer shed and regrow their entire antlers at an astonishing rate. This process actually represents the only known case of complete appendage regeneration in a mammalian species, making it a valuable tool to study why regeneration is limited in most mammals as well as how we can change that.
When a deer sheds its antlers, it is left with a structure known as the pedicle, the location of regeneration. Early research determined that the pedicle is responsible for antler regrowth by transplanting it onto another area of the deer and observing that a new antler will sprout. Lining the pedicle is a layer known as the periosteum, which contains a population of cells that can be induced to differentiate into multiple cell lineages such as bone, muscle, and nervous tissue. These multipotent cells are able to supply all the cell types necessary to regenerate each component of the antler: blood vessels, nerves, bone, cartilage, and skin, but must be closely associated in a niche with the surrounding skin of the pedicle in order for regeneration to occur.
Researchers are currently working to uncover the molecular signals responsible for antler regeneration and thus potential therapeutic uses. Published in Genes & Genomics this year, Dr. Dong Zheng and colleagues conducted microRNA profiling of newly-regenerated antler cartilage. Although they identified many regeneration-related genes specific to antlers, there were also more conserved sequences present that are found in other mammals, including humans. Inducing the expression of these genes in a tissue that normally doesn’t regenerate could help to enhance the healing process. Furthermore, antler stem cells can be isolated for use as an in vitro model system. A group in Poland has shown that transplanting either the cells themselves or the cell supernatant (fluid in which cells are cultured during growth) can enhance regeneration of an injured mandible in rabbits. This effect is likely due to the presence of cell-secreted growth factors. If we can determine which signals initiate and direct antler regeneration, we can potentially manipulate the expression of these molecules in other systems to encourage regeneration of tissues such as cartilage or skin.
Another intriguing mystery of antler regeneration is what signals are involved in structural patterning? How do the resident stem cells direct the desired antler structure, and how do they know when to cease growth? Despite the rapid regeneration of antlers, the process does not appear to resemble the uncontrolled cell division seen in tumour formation. To answer these questions, mathematical models have been created to predict cell behaviour during regeneration. One model suggests that certain cells may retain a memory of their former position and act as coordinator cells to conduct the growth and position of surrounding cell cohorts, although at this point the mechanism is unknown.
While many aspects of antler regeneration remain a mystery to researchers and we’re not likely to hear a new holiday classic about Rudolph’s fuzzy regenerating antlers any time soon, we can still appreciate this remarkable process as a unique tool in the quest to understand mammalian tissue regeneration.