Abstract
High numbers of adult stem cells are still required to improve the formation of new vessels in scaffolds to accelerate dermal regeneration. Recent data indicate a benefit for vascularization capacity by stimulating stem cells with lipopolysaccharide (LPS). In this study, stem cells derived from human skin (SDSC) were activated with LPS and seeded in a commercially available dermal substitute to examine vascularization in vivo. Besides, in vitro assays were performed to evaluate angiogenic factor release and tube formation ability. Results showed that LPS-activated SDSC significantly enhanced vascularization of the scaffolds, compared to unstimulated stem cells in vivo. Further, in vitro assays confirmed higher secretion rates of proangiogenic as well as proinflammatoric factors in the presence of LPS-activated SDSC. Our results suggest that combining activated stem cells and a dermal substitute is a promising option to enhance vascularization in scaffold-mediated dermal regeneration.
Highlights
The outer barrier of the human body skin has various important functions such as protection from pathogens and thermoregulation
An immunocytochemical staining revealed the expression of toll-like receptor 4 (TLR-4) on the surface of human skin-derived stem cells (SDSC), after cells had been successfully isolated from human full skin biopsies
Thrombospondin-2, vascular endothelial growth factor (VEGF), TGFb and Angiopoietin-1 showed a tendency towards an upregulation (Fig 3). Since these results indicated a proangiogenic effect exerted by stimulated Skin-derived stem cells (SDSC), a tube formation assay was performed to investigate the respective culture supernatant regarding its potential to possibly support the formation of capillary-like structures
Summary
The outer barrier of the human body skin has various important functions such as protection from pathogens and thermoregulation. Split-skin grafting remains the “gold standard” for treating damaged areas due to its easy and fast harvesting, availability is limited [1]. Restoring the full barrier function and mobility of the skin will not occur unless dermal and epidermal layers are completely rebuilt [2]. Solely split-skin grafting is insufficient for a good functional and esthetical outcome. Skin tissue engineering has emerged as an alternative therapeutic option. In this context, three-dimensional biodegradable scaffolds are serving as a backbone for infiltrating cells and new vessel formation. Besides cadaver donor skin, certified dermal replacement
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