Exploiting reindeer to understand the mechanisms of skin regeneration and inform development of novel regenerative therapeutics
Description: More than 14 million severe skin wounds (burns, trauma, ulcers) are treated annually in North America. The annual cost of wound care in Canada is >$4 billion. Deficiencies in wound healing stem from an inability to regenerate functional dermis and the tendency of dermal fibroblasts to form scar. Scar tissue is dysfunctional and associated with chronic pain, immobility, and physical disfigurement, which are typically lifelong. Therapies that prevent scarring, by promoting dermal regeneration, would have tremendous clinical value. We pioneered the use of captive reindeer to study adult mammalian skin regeneration. After injury, antler skin (velvet) undergoes 'scarless' healing, whereas identical wounds in back skin form fibrotic scar (Sinha et al, Cell, 2022). Regenerative wounds are associated with: 1) re-activation of development-associated genes in velvet fibroblasts, and 2) altered immune recruitment that consequently provides distinct instructions to wound-healing fibroblasts. These insights provide a 'blueprint' of the cellular composition and signaling ensembles that enable skin regeneration in adult mammals. Building on these findings, we will test the hypothesis that recreating the velvet wound microenvironment and/or purposefully activating pro-regenerative genes in dermal fibroblasts can limit scar and enable skin regeneration. Aim 1 - To ask whether activating pro-regenerative gene networks in dermal fibroblasts can enhance skin regeneration. Aim 2 - To ask how velvet dermal fibroblasts influence local immune cell function to alter wound healing outcomes. Aim 3 - To characterize the cellular composition and signaling dynamics during acute human wound healing and how this compares to regenerative healing in reindeer. Impact: This project will provide new knowledge about how to prevent formation of scar and potentially develop novel therapeutics to enable endogenous skin regeneration and restoration of function following severe skin injury or disease.
Amount: CA$100,000
Funding type: research
Funder scheme: Project Grant - Priority Announcement: Musculoskeletal Health and Arthritis - Skin
Start date: 2023-10-01
End date: 2024-09-30
Investigator: Jeffrey Biernaskie
Institution: University of Calgary
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 190392_1
OpenAlex ID: G4364033758