title: The role of biomaterials in the direction of mesenchymal stem cell properties and extracellular matrix remodelling in dermal tissue engineering.
abstract: Recently, a new generation of dermal equivalents (DE) was presented which are solely generated on a human fibroblast-derived dermal matrix. Since human mesenchymal stem cells from bone marrow (BM-MSC) and Wharton's Jelly of the umbilical cord (UC-MSC) are characterised by a distinct biosynthetic and paracrine activity, they are an appealing alternative approach for generating cell-based DE. This study compares the epithelial-mesenchymal interaction and extracellular matrix (ECM) remodelling of cell-based and collagen-based DE using fibroblasts, BM-MSC or UC-MSC, respectively, in co-culture with the keratinocyte cell line HaCaT. While fibroblast-based DE exhibit normal matrix synthesis, proliferation and differentiation of keratinocytes, mesenchymal stem cell-based DE resulted in excessive production of inhomogenous matrix aggregates, loss of polarisation of the epidermal cell layer and an inconstant paracrine activity. In contrast, collagen-embedded MSC revealed a homogenous growth pattern as well as a constant expression of growth factors and ECM proteins without a negative influence on the epidermal layer as shown by histology, electron microscopy, immunohistochemistry and realtime-RT-PCR. These results indicate the necessity of an instructive biomaterial-based scaffold to direct stem cell differentiation, proliferation, paracrine activity as well as regulation of ECM deposition.
authors.affiliation: Institute of Pathology, Medical Faculty RWTH Aachen University, Aachen, Germany.
authors.forename: Rebekka K
authors.initials: RK
authors.lastname: Schneider
authors.forename: Julia
authors.initials: J
authors.lastname: Anraths
authors.forename: Rafael
authors.initials: R
authors.lastname: Kramann
authors.forename: Jörg
authors.initials: J
authors.lastname: Bornemann
authors.forename: Manfred
authors.initials: M
authors.lastname: Bovi
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.forename: Sabine
authors.initials: S
authors.lastname: Neuss
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D020405:Dermis / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D020782:Matrix Metalloproteinases