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Differentiation of Human Dermal Fibroblasts: a New Tool in Vascular Tissue Engineering
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
2009 (English)Licentiate thesis, comprehensive summary (Other academic)Alternative title
Celler från huden kan hjälpa patienter med kärlsjukdomar (Swedish)
Abstract [en]

Tissue engineering is an expanding field, which focuses on the development of func-tional substitutes for damaged tissues. A limitation in this field is difficulties with obtaining autologous cells. Recent research has shown the presence of cells with multilineage-potential within the connective stroma of the skin. In line with this, a potential plasticity inherent in human dermal fibroblasts has been demonstrated. The overall aim of this study was to investigate if human dermal fibroblasts can be used as a cell source for vascular tissue engineering. Differentiation towards an endothelial cell-like phenotype was induced by culturing dermal fibroblasts in endothelial growth medium. By utilizing in vitro cell culture models, the capacity of different types of serum and serum constituents in inducing a phenotypic shift in fibroblasts was investi-gated. To clarify the mechanisms behind this phenotypic shift and to eliminate the risk of having growth of residual endothelial cells in the cultures, both normal dermal fibroblasts and single-cell clone fibroblasts were used. Our results demonstrated that presence of human serum caused fibroblasts and single-cell clone fibroblasts to express vWf, to incorporate fluorochrome-labeled low-density lipoprotein, and to start form-ing capillary-like networks. As an initial step in using these cells in tissue engineering, their ability to endothelialize a surface in vitro was studied. Cells cultured in either fibroblast or endothelial growth medium were seeded on scaffolds. Differentiation was confirmed by western blotting and immunohistochemistry using antibodies directed towards vWf, ve-cadherin, eNOS, and bradykinin receptor B2. The results revealed that endothelial differentiated fibroblasts cultured on scaffolds showed histological resem-blance to endothelial cells, and expressed molecules indicative of an endothelial phenotype. In conclusion, the results presented in this study indicate a possibility to induce differentiation of human dermal fibroblasts towards an endothelial cell-like phenotype. Consequently, these data suggests that human dermal fibroblast may be a novel cell source for vascular tissue engineering.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2009. , 59 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 99
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-20319ISBN: 978-91-7393-617-0 (print)OAI: oai:DiVA.org:liu-20319DiVA: diva2:233963
Presentation
2009-08-25, Hagdalsalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 09:00 (Swedish)
Supervisors
Note

In the printed version the series number of this Licentiate thesis is 98. In the electronic version it has been corrected to 99.

Available from: 2009-09-03 Created: 2009-09-03 Last updated: 2013-07-04Bibliographically approved
List of papers
1. Human Dermal Fibroblasts and Single-Cell Clone Fibroblasts Have theCapacity to Alter Their Phenotype Towardsan Endothelial-Like Cell type
Open this publication in new window or tab >>Human Dermal Fibroblasts and Single-Cell Clone Fibroblasts Have theCapacity to Alter Their Phenotype Towardsan Endothelial-Like Cell type
2009 (English)In: European Cells and Materials, ISSN 1473-2262Article in journal (Other academic) Submitted
Abstract [en]

We investigated the capacity of normal human dermal fibroblasts to alter their phenotype into an endothelialcell-like phenotype. By utilising in vitro cell culture models, the part played by different types of serum andmedium constituents in inducing a phenotypic change of fibroblasts was investigated. The experiments usedprimary cultures of human endothelial cells, human dermal fibroblasts and single-cell clone fibroblasts. Thelatter cell type was obtained by clonal expansion using a micromanipulator technique. The results showed thatthe presence of human serum in the cell culture medium caused both types of fibroblasts to express vonWillebrand factor, to incorporate fluorochrome-labelled LDL, and to start forming capillary-like networks in asimilar way to endothelial cells. The phenotypic shift was detectable after 4 days of cell culture and reached amaximum after 7-10 days. To our knowledge this is the first report to describe differentiation of humanfibroblasts towards an endothelial cell-like phenotype. The results also show that the underlying mechanism ofthe phenotypic shift is a change in gene expression in the dermal fibroblasts and not fusion between different celltypes. Collectively, the present results indicate that human dermal fibroblasts may be a novel cell source forcreating vascular endothelium.

Keyword
Differentiation, Endothelial cells, Fibroblasts, Single-cell clone fibroblasts, Tissue engineering
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19713 (URN)
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2009-09-03Bibliographically approved
2. Human Dermal Fibroblasts: A Potential Cell Source for Endothelialization of Vascular Grafts
Open this publication in new window or tab >>Human Dermal Fibroblasts: A Potential Cell Source for Endothelialization of Vascular Grafts
2009 (English)In: Annals of Vascular Surgery, ISSN 0890-5096, Vol. 23, no 5, 663-674 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recently, there has been an intense ongoing search for suitable cell sources for vascular tissue engineering. Previous studies report that cells with multilineage potential have been found within the connective stroma of the skin. In line with this, preliminary data from our group suggest that human dermal fibroblasts have the capacity to alter their phenotype into an endothelial cell-like phenotype in vitro. As a first step in using these cells in vascular tissue engineering, we investigated their ability to form an endothelial cell-like layer on a scaffold in vitro. Furthermore, we studied the possibility of seeding dermal fibroblasts on a scaffold and later commencing with induction toward an endothelial cell-like phenotype. METHODS: Cells cultured in either normal fibroblast medium or endothelial induction medium were seeded on a gelatin-based scaffold. To study the organization of cells, routine staining was performed. Differentiation was confirmed by Western blotting and immunohistochemistry with antibodies directed toward molecules commonly used to identify endothelial cells. RESULTS AND CONCLUSION: Our data support that human dermal fibroblasts differentiated toward endothelial cell-like cells prior to seeding showed histological resemblance to mature endothelial cells, while fibroblasts seeded and later induced into endothelial differentiation grew in multilayer. However, expression of various surface molecules indicative of an endothelial phenotype was seen using both techniques. In conclusion, the results presented in this study indicate that human dermal fibroblasts differentiated toward an endothelial cell-like phenotype may be a novel cell source for endothelialization of vascular grafts.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19714 (URN)10.1016/j.avsg.2009.03.007 (DOI)19576728 (PubMedID)
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2009-09-26Bibliographically approved

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