Epithelial Differentiation of Human Skin Equivalents After Grafting Onto Nude Mice

Engraftment of umbilical cord epithelial cells in athymic mice: in an attempt to improve reconstructed skin equivalents used as epithelial composite

“…In this animal model, engraftment reaches a state of equilibrium around 2 weeks after transplantation [18,10,22]. We achieved complete basement membrane formation, which is consistent with the results reported from the earlier experiments in animal models [24,37,38]. Grafted keratinocytes differentiated faster than UCE cells but at 2 weeks both epithelia properly expressed stratified epithelial structures and markers by morphological 36 B. Sanmano et al Fig.…”

“…4o and s). In corroboration of several previous studies [23,24], we observed staining to be in linear alignment along the basement membrane zone at 2 weeks after transplantation in both grafted keratinocytes ( Fig. 4n and r) and grafted UCE cells (Fig.…”

“…A 2.5 cm  2.5 cm full thickness skin area was excised down to the muscle on the back of the mouse, and one type of epithelial skin equivalent complex, seeded with either keratinocytes or UCE cells, was placed on the raw surface. A combi-ring-dish (CRD; Renner GmbH, Dannstadat, Germany) chamber was installed in the wound and stitched to the mouse skin [21][22][23][24][25]. For the first seven days the chambers were kept closed with the caps.…”

“…However, an animal model, such as a mouse model, is a more appropriate system than an in vitro system because the transplanted epithelial cells, seeded on artificial matrices such as collagen gels populated with fibroblasts, have direct contact with mouse tissue [21][22][23][24][25], creating a balance of interactions that cannot be entirely achieved using an in vitro model [26].…”

Development of Microfabricated Dermal Epidermal Regenerative Matrices to Evaluate the Role of Cellular Microenvironments on Epidermal Morphogenesis

“…The formation of papillary projections and rete ridges between epidermal and dermal components has been reported after transplantation of composite bioengineered skin substitutes; however, formation does not always occur, and when it has been reported, inconsistencies in the time of formation and the size of rete ridges exist. [35][36][37][38][39] Furthermore, bioengineered skin substitutes lacking the 3D microenvironment at the DEJ have been reported to be fragile and prone to accidental separation of epithelial and dermal components during handling. 40 In this study, we developed a mDERM that contains the 3D microenvironment found at the DEJ and evaluated the role of the native microenvironment in guiding the integration of transplanted cells and their derivatives into a functional tissue equivalent.…”