Abstract
CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26+ fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation.
Highlights
CD26, known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin
CD26, known as dipeptidyl peptidase IV, is a multifunctional, membrane-bound protein playing a significant role in the wound healing and scarring processes in the skin of mice[17,25]
We analyzed in-depth the expression pattern of CD26 in human skin
Summary
CD26, known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. Dermoepidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Fibroblasts are the most prevalent cell type in the dermis They are embryonically derived from the mesenchyme and synthetize and deposit certain components of the extracellular matrix (ECM)[1,2]. The papillary dermis is a superficial region located just underneath the dermo-epidermal junction It is characterized by the presence of thin and poorly organized collagen type I bundles that provide structural support to the overlying epithelium. Haydont et al have conducted genome-wide molecular profiling of papillary and reticular
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