Comparative models of Regeneration and fibrosis
While regeneration in mammals is rare, some animals and some tissues are better at regaining form and function after injury than others. We compare injury models to find pathways that lead to regeneration and pathways that lead to scar formation. Our goal is to develop new therapies that can promote regeneration in diseased or damaged human tissues.
Our main focus is on neuropeptides released from injured and re-growing nerves and on growth factors released by immune cells that populate the injury.
COMPARATIVE MODELS IN MAMMALS
THE DIGIT: Mice and humans are able to regenerate the tip of their fingers and toes after an amputation injury. Our work uncovers pathways to answer how the bone and skin of the digit tip regenerates and understand why more proximal amputations form a scar.
SPINY MOUSE VERSUS LAB MOUSE:
THE EAR PINNA: A 4 mm hole
through a human or mouse ear
forms a scar and that missing
tissue will never be replaced.
The African Spiny Mouse,
however, is unique in that it can
regenerate the 4 mm of missing
tissue which includes
cartilage, hair follicles, muscle,
USING MACROPHAGES TO GUIDE WOUND HEALING
Macrophages ("big eaters") are the ultimate clean up grew of the body. After injury, macrophages swarm the area and remove any foreign debris or dead cells. Macrophages also orchestrate the healing response by recruiting new cells, promoting cell division, and promoting new collagen deposition.
Our work aims to identify different macrophage populations that my be able to guide tissue healing away from scar formation and toward regeneration. Our ultimate goal is to use pro-regenerative macrophages to promote regeneration in humans.
TESTING NEUROPEPTIDES AS ANTI-FIBROTIC THERAPIES
Nerves secrete many factors after injury. These factors can promote cell division, collagen production, or tissue growth. With our models, we are able to identify factors that are specific to healing with scar and those that are specific to regeneration. We can then test how changing different neuropeptides affects healing outcome.
Nerves regrowing into the regenerating Spiny mouse ear pinna. Gawriluk et al. Nat Comm 2017.