Decellularized Keloid Matrix As A Novel Three-Dimensional Model For Studying Cellular Behavior Of Abnormal Keloid Fibroblasts
Silvian Tan, Ardeshir Bayat.
University of Manchester, Manchester, United Kingdom.
BACKGROUND The pathophysiology of keloids involves a complex orchestrated series of processes, which has yet to be explored and fully defined. In particular, the interaction between the various populations of cells within keloids and the keloid matrix is unclear, with many matrix molecules having been implicated in its development as a result of dysregulated homeostasis. Nevertheless, research in keloids is largely hindered by the lack of effective animal models. Despite the use of different materials and animals to model the disease, there is a profound difficulty in exploring the cell-matrix interactions in keloids as a function of the keloid micro-environment. This is important as the role of mechanobiology has been increasingly shown to be crucial in the pathogenesis of many other diseases. METHODS Using tissue engineering methods, we hereby propose a novel model using decellularized scaffolds to study the behavior of keloid fibroblasts in a three-dimensional environment which retains features of these mechanical properties. Punch biopsies obtained from decellularized keloid and normal skin samples were seeded with keloid and normal dermal fibroblasts and subsequently maintained for 14 days. The proliferation rates of keloid fibroblasts in the two groups (n=5 each) were measured and compared at days 3, 7 and 14 using PrestoBlue. RESULTS We found that keloid fibroblasts exhibited significantly higher proliferation rates in the keloid scaffold group. Our results suggest that there may be structural as well as intrinsic properties within the keloid matrix, which are absent in normal skin, driving the accelerated growth of keloid fibroblasts following disease activation. CONCLUSIONS More importantly, we have developed a viable model to study keloid behavior in a three-dimensional environment which closely resemble their original matrix, thereby facilitating further study of cell-matrix interaction in more detail.
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