Hair follicle transplantation: implications for cell migration and wound healing

© 2016 Dr. Azar AsgariChronic wounds are a major problem in the health care system. The increasing incidence of obesity and diabetes and longer life expectancy are adding to the burden. Treatment options are currently limited indicating needs for new treatment modalities. Impaired innate healing response is the main characteristic of chronic wounds. In recent years, there has been a focus on stem cell therapy and tissue engineering as an alternative treatment for chronic wounds to replace the damaged tissue with cells that possess a normal injury response. The hair follicle’s continuous cycling and their response to trauma stimulation, indicate a strong regenerative potential. It has been shown that hair follicles participate in wound re-epithelialization and respond to skin injury by promoting skin innervation and vascularization. This dissertation explores the potential of hair follicle transplantation to enhance wound healing. It was hypothesized that hair follicle transplantation can promote healing in skin wounds. Whole hair follicle were isolated and re-established in the wound site where they preserved their structure and function. This approach exploits the normal endogenous function of hair follicle cells to enhance skin wound healing. First, a vibrissae follicle transplantation technique was established and optimised in nude mice. Using donor follicles from GFP transgenic mice made it possible to investigate cell trafficking from transplanted follicles during epidermal and dermal repair. Transplanted vibrissae follicles integrated normally into the host epithelium and ninety percent of grafted vibrissae produced a hair shaft. The GFP labelled cells were confined to the transplanted hair follicles and were not found in the interfollicular epidermis. It was then possible to identify migrating hair follicle cells from recipient inter-follicular epidermis in lineage tracing wound experiments. Healing responses were then compared in excisional wounds with and without adjacent transplanted follicles. My findings re-confirmed that hair follicle cells participated in wound re-epithelialisation. Neighbouring transplanted follicles accelerated wound closure. Wounds adjacent to transplanted follicles also showed four times higher nerve density in the granulation tissue than the wounds without adjacent follicular transplants. There was no significant difference in capillary density and macrophage density in wounds with and without hair transplants. I also conducted a preliminary investigation of incisional wounds perpendicular or parallel to transplanted follicles, to compare hair follicle cell migration from damaged and intact hair follicles. In these experiments, intact hair follicles participated only in the epidermal component of wound healing and cells migrated from transplanted hair follicles to the healing dermis only when the hair follicles were cross-sectioned. The results of this dissertation indicated that re-epithelialization and promotion of innervation were possible mechanisms by which transplanted follicles contributed to wound healing. These findings lay the foundations for using follicular transplantation to promote healing in chronic or neuropathic wounds and peripheral nerve injuries. In addition, damage to hair follicles may be a starting signal for migration and participation of hair follicle cells in the repair of dermis, which may subsequently influence the healing outcome