Journal
DIFFERENTIATION
Volume 79, Issue 3, Pages 182-193Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2010.01.005
Keywords
Mesenchymal stem cells; Wharton's jelly; Skin tissue engineering; Dermal equivalents; Myofibroblasts; Extracellular matrix
Categories
Funding
- Interdisciplinary Centre of Clinical Research IZKF BIOMAT.'' within the Faculty of Medicine at the RWTH Aachen University [VVB-110f]
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During early embryogenesis, mesenchymal cells arise from the primitive epithelium and can revert to an epithelial phenotype by passing through mesenchymal-to-epithelial transition (MET). Mesenchymal stem cells (MSC) of the Wharton's Jelly of the umbilical cord (UC-MSC) express pluripotency markers underlining their primitive developmental state. As mesenchymal stem cells from bone marrow (BM-MSC) possess a strong propensity to ameliorate mesenchymal tissue damage, UC-MSC might also be able to differentiate into cells apart from the mesoderm, allowing replacement of ectodermal and mesodermal tissues. In this study, we analysed the possible epidermal differentiation of UC-MSC on dermal equivalents (DEs) consisting of collagen I/III with dermal fibroblasts and subjected to the culture conditions for tissue engineering of skin with keratinocytes. The culture conditions were further modified by pre-treating the cells with 5-azacytidine or by supplementing the medium with all trans retinoic acid. Interestingly, a subpopulation of UC-MSC (29%) co-expressed pan-cytokeratin (epithelial marker; pan-CK) and vimentin (mesenchymal marker) after isolation. Under the three-dimensional conditions of skin, the number of pan-CK(+)-cells increased to >30% after 21 days of cultivation, while under osteogenic culture conditions the cells were pan-CK-negative, thus showing the influence of the artificial niche. Nevertheless, the pan-CK-expression was neither accompanied by typical epithelial morphology nor expression of other epidermal markers. The pan-CK-detection can be explained by the expression of cytokeratins in myofibroblasts. UC-MSC expressed alpha-smooth muscle actin after isolation and displayed all features of functional myofibroblasts like morphology, cell-mediated contraction of a collagen gel and production of components of the extracellular matrix (ECM). The treatment with all trans retinoic acid or 5-azacytidine could neither induce an epidermal differentiation nor enhance the myofibroblastic differentiation. Concluding, UC-MSC might be an interesting cell source to support the regeneration of wounds by their differentiation into myofibroblasts and their extensive synthesis of ECM components. (C) 2010 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
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