Longitudinal Analysis of Disease Site Activities Impairing Wound Healing in Epidermolysis Bullosa and Development of Therapeutic Strategies
[Technical Report, Annual Report]
Thomas Jefferson University
Pagination or Media Count:
Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa RDEB. At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches. To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks. We developed a non-invasive approach for sampling and analysis of wound-associated constituents using wound-covering bandages. Cellular and molecular components from seventy-six samples collected from early, established and chronic RDEB wounds were evaluated by FACS-based immuno-phenotyping and ELISA. Our cross-sectional and longitudinal analysis determined that progression of RDEB wounds to chronic state is associated with the accumulation up to 90 ofCD16 CD66b mature neutrophils, loss of CD11b CD68 macrophages, and a significant increase up to 50 in a number ofCD11c CD80 CD86 activated professional antigen presenting cells APC. It was also marked by changes in activated T cells populations including a reduction of CD45RO peripheral memory T cells from 80 to 30 and an increase up to 70 in CD45RA effector T cells. Significantly higher levels of MMP9, VEGF-A and cathepsin G were also associated with advancing of wounds to poorly healing state. Our data demonstrated that wound-covering bandages are useful for a non-invasive sampling and analysis of wound-associated constituents and that transition to poorly healing wounds in RDEB patients as associated with distinct changes in leukocytic infiltrates, matrix-remodeling enzymes and pro-angiogenic factors at wound sites.
- Anatomy and Physiology