NHMRC Career Development Fellowship (Clinical; Level 1): Stem and progenitor cell contribution to skin wounds and homeostasis (2012–2015)
The skin is a complex tissue containing a broad variety of cell types. Its main function is to establish a lipido-protein barrier that requires the permanent contribution of epidermal stem cells to the pool of amplifying keratinocytes. Disruption of this homeostasis by wounds is a major health issue and for many years now, cultured keratinocytes or epidermal stem cells have been provided in cellular therapy for wounds. However, this approach results in scars that are devoid of hair follicle and sebaceous glands and can restrict movement. Most importantly, in a large group of patients with co-morbidities such as diabetes or arterial or veinous diseases, wounds remain open chronically and do not respond to epidermal stem cell therapy. Wound management, especially chronic wounds, represents a major burden for health systems globally costing $2.6 billion annually in Australia. Besides keratinocytes, wound closure has been shown to depend on the different components of the underlying dermis: inflammatory cells, fibroblasts and endothelial cells. Based on preliminary data and our experience in perinatal and fetal stem cells we propose that:
-Modulation of populations of macrophages, endothelial progenitors or mesenchymal cells in the wound bed will significantly affect healing.
-The use of primitive populations of mesenchymal progenitors can drive epidermal stem cells towards skin regeneration rather than scarring
Our aims are:
1-Modulation of macrophage subpopulations during skin wound healing to reduce fibrosis and accelerate closure of chronic wounds
2-Identification of fetal mesenchymal populations to be used as equivalent dermis to promote regeneration rather than healing
3- Fetal endothelial progenitor cell therapy to improve chronic wound vascularisation and healing
These experiments represent a global approach to skin wound management and will identify new therapeutic targets and new cellular therapies to be used off the shelf in skin wounds.