This thesis describes the development of human skin equivalents that show characteristics of skin aging. The type of skin equivalent used was a fibroblast derived matrix equivalent, in which... Show moreThis thesis describes the development of human skin equivalents that show characteristics of skin aging. The type of skin equivalent used was a fibroblast derived matrix equivalent, in which the dermal compartment is generated by fibroblasts and thus is fully of human origin. Two strategies are described to include characteristics of skin aging in skin equivalents. Firstly, skin equivalents generated with senescent fibroblasts show some signs of skin aging, like increased MMP production and increased epidermal stress. However, some characteristics, like reduced epidermal turnover, are noticably lacking. The second strategy involved using papillary and reticular fibroblasts. During aging the papillary dermis shrinks in size, which leads to a relative increase of reticular fibroblasts over papillary fibroblasts. Equivalents generated with reticular fibroblasts showed reduced epidermal turnover and disturbed epidermal differentiation compared to equivalents generated with papillary fibroblasts. In addition, we showed that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. This leads to the hypothesis that during skin aging papillary fibroblasts differentiate into reticular fibroblasts, leading to changes in both dermal and epidermal homeostasis. Further research with equivalents described in this thesis can further elucidate the role of papillary and reticular fibroblasts during skin aging. Show less
Drielen, K. van; Gunn, D.A.; Noordam, R.; Griffiths, C.E.M.; Westendorp, R.G.J.; Craen, A.J.M. de; Heemst, D. van 2015
