Human dermal fibroblasts: a potential cell source for endothelialization of vascular grafts.
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.


CONCLUSIONS
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.
Karlsson
Lisa K
LK
Department of Clinical and Experimental Medicine, Center for Tissue Engineering, University Hospital of Linköping, Linköping, Sweden. lisa.karlsson@liu.se
Junker
Johan P E
JP
Grenegård
Magnus
M
Kratz
Gunnar
G
D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D011474:Prosthesis Design; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014841:von Willebrand Factor / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D005780:Gelatin; D052250:Nitric Oxide Synthase Type III; D043782:Receptor, Bradykinin B2; D014841:von Willebrand Factor; D000099152:Cadherin 5; C496314:NOS3 protein, human