Dreidimensionales epidermis-ähnliches Wachstum humaner mesenchymaler Stammzellen auf dermalen Äquivalenten : Einfluss der experimentellen Kulturbedingungen auf Differenzierung, Migration und funktionelles Verhalten

Human mesenchymal stem cells (hMSC) are able to differentiate into mature cells of various mesenchymal tissues. Recent studies have reported that hMSC may even give rise to cells of ectodermal origin. This indication of plasticity makes hMSC a promising donor source for cell-based therapies. This study explores the differentiation potential of hMSC in a tissue-specific microenvironment simulated in vitro. Human MSC were cultured air-exposed on dermal equivalents (DEs) consisting of collagen types I and III with dermal fibroblasts and subjected to similar conditions used for tissue engineering of skin with keratinocytes. Culture conditions were additionally modified by pre-treating the cells with 5-azacytidine or supplementing the medium with all trans retinoic acid. Human MSC were capable of adaptation to epidermis-specific conditions without losing their mesenchymal multipotency. However, despite the viability and evident three-dimensional epidermis-like growth pattern, hMSC showed a persistent expression of mesenchymal but not of epithelial markers, thus indicating a lack of epidermal (trans) differentiation. Further, electron microscopy and immunohistochemical analyses demonstrated that hMSC cultured under epidermis-specific conditions adopted myofibroblastic phenotype and function, promoted in particular by air-exposure. In conclusion, multipotent hMSC failed to differentiate into E-cadherin- or cytokeratin-expressing cells under optimized organotypic culture conditions for keratinocytes but differentiated into myofibroblast-like cells contracting the extracellular matrix, a phenomenon which was enhanced by retinoic acid and 5-azacytidine. These results indicate that hMSC might contribute to wound healing processes by extracellular matrix reorganization and wound contraction but not by differentiation into keratinocytes.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Schneider-Kramann, Rebekka Katharina Marita

Contributors dc:contributor

• Knüchel-Clarke, Ruth

• info:eu-repo/classification/ddc/610
• Adulte Stammzelle
• Stammzelle
• Medizin
• mesenchymale Stammzellen
• Hautäquivalent
• tissue engineering
• Keratinozyten
• Myofibroblasten
• mesenchymal stem cells
• dermal equivalent
• keratinocytes
• myofibroblast

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112685%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50129