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Human Dermal Fibroblasts and Single-Cell Clone Fibroblasts Have theCapacity to Alter Their Phenotype Towardsan Endothelial-Like Cell type
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
2009 (English)In: European Cells and Materials, ISSN 1473-2262, E-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.

Place, publisher, year, edition, pages
2009.
Keyword [en]
Differentiation, Endothelial cells, Fibroblasts, Single-cell clone fibroblasts, Tissue engineering
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-19713OAI: oai:DiVA.org:liu-19713DiVA: diva2:227685
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Human Dermal Fibroblasts in Tissue Engineering
Open this publication in new window or tab >>Human Dermal Fibroblasts in Tissue Engineering
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The loss or failure of tissues and/or organs is one of the most frequent problems in modern healthcare. The field of tissue engineering applies the principles of biology and engineering in order to develop functional substitutes for damaged tissues. Tissue engineering contains elements of medicine, material science and engineering with major components in focus being cells, biomaterials and soluble factors. All three components may be required for the development of clinical treatments.

The usage of autologous tissue specific cells for clinical treatment is often not feasible due to poor growth kinetics or unstable phenotypes of the cells. Furthermore, lack of availability of healthy tissue that can be biopsied is a major problem in many applications. One approach to overcome this problem is to use adult stem cells which have the capacity to give rise to several different cell types. Although promising, adult stem cells have major impediments for use in several tissue engineering applications. The difficulties associated with harvest, culture and storage render problems in the development of clinically relevant procedures.

During the last years, the inherent plasticity of differentiated somatic cells has been demonstrated. One of the easiest human cell types to obtain, expand and store is the dermal fibroblast. Recent reports indicate that dermal fibroblasts can be induced to differentiate towards several distinct mesenchymal lineages in vitro.

The main aim of this thesis was to investigate the inherent stem cell plasticity of human dermal fibroblasts and explore their possible usefulness in tissue engineering applications. The papers included in this thesis employ routine and immunohistochemical staining, enzyme activity assay, analysis of low density lipoprotein incorporation, capillary-like network formation assay and full expression micro array analysis.

Fibroblasts were shown to differentiate towards adipocyte, chondrocyte, endothelial and osteoblast-like cell types in vitro. The differentiation from fibroblasts to myofibroblasts in burn scar tissue upon stimulation by mechanical tension was also demonstrated. Adipogenic, chondrogenic and osteogenic induced fibroblasts display the upregulation of several genes associated with adipocytes, chondrocytes and osteoblasts.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 56 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1133
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19716 (URN)978-91-7393-618-7 (ISBN)
Public defence
2009-08-27, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2009-09-15Bibliographically approved
2. Differentiation of Human Dermal Fibroblasts: a New Tool in Vascular Tissue Engineering
Open this publication in new window or tab >>Differentiation of Human Dermal Fibroblasts: a New Tool in Vascular Tissue Engineering
2009 (English)Licentiate thesis, comprehensive summary (Other academic)
Alternative title[sv]
Celler från huden kan hjälpa patienter med kärlsjukdomar
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:nbn:se:liu:diva-20319 (URN)978-91-7393-617-0 (ISBN)
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

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Karlsson, Lisa K.Junker, JohanGrenegård, MagnusKratz, Gunnar

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