Grant: Project Grant

More than 14 million severe skin wounds (burns, trauma, ulcers) are treated each year in North America. The consequence is chronic pain, immobility, disfigurement and in many cases infection leading to further medical complication or death, particularly in the elderly. The annual societal cost of wound care in Canada alone is estimated at $4 billion. One of the primary reasons that wounds do not heal is due to an inability to regrow healthy dermis and a tendency to form fibrous scar tissue. The dermis provides essential nutrients and mechanical support to the overlying epidermis and skin appendages (hair follicles, glands, nerves, blood vessels) embedded within it. Strategies to regrow new functional dermis and its appendages are desperately needed to reduce health care costs and to restore quality of life after skin injury, particularly in the elderly. An attractive approach is to stimulate stem cells that reside in adult skin. Our preliminary studies identified two different populations of dermal stem cells that are activated in response to injury and are recruited into skin wounds where they typically form scar. However, under some circumstances, these same cells can become regenerative, rather than scar-forming, even initiating formation of new hair follicles and healthy fat cells within the wound. Thus, enhancing dermal stem/ cell function could limit formation of scar and improve skin healing. To realize this clinical potential, we will: 1) Characterize the signals within the wound that drive regenerative versus scar-forming stem cell responses 2) Identify mechanisms to effectively stimulate and recruit dermal stem cells after injury 3) Determine how old age changes dermal stem cell response to injury. Our goal is to identify drug targets that could be used to modulate dermal stem cell response after injury in order to improve the quality of wound healing, thereby improving functional outcomes for Canadians suffering severe skin injury or disease.