Characterization of vasculogenic potential of human adipose-derived endothelial cells in a three-dimensional vascularized skin substitute

Klar, Agnes S. and Güven, Sinan and Zimoch, Jakub and Zapiórkowska, Natalia A. and Biedermann, Thomas and Böttcher-Haberzeth, Sophie and Meuli-Simmen, Claudia and Martin, Ivan and Scherberich, Arnaud and Reichmann, Ernst and Meuli, Martin. (2016) Characterization of vasculogenic potential of human adipose-derived endothelial cells in a three-dimensional vascularized skin substitute. Pediatric Surgery International, 32 (1). pp. 17-27.

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Official URL: http://edoc.unibas.ch/53078/

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The need for clinically applicable skin substitutes continues to be a matter of fact. Hypothetically, a laboratory grown autologous skin analog with near normal architecture might be a suitable approach to yield both satisfactory functional and cosmetic long-term results. In this study, we explored the use of human endothelial cells derived from freshly isolated adipose stromal vascular fraction (SVF) in a three-dimensional (3D) co-culture model of vascularized bio-engineered skin substitute.; The SVF was isolated from human white adipose tissue samples and keratinocytes from human skin biopsies. The SVF, in particular endothelial cells, were characterized using flow cytometry and immuofluorescence analysis. Endothelial and mesenchymal progenitors from the SVF formed blood capillaries after seeding into a 3D collagen type I hydrogel in vitro. Subsequently, human keratinocytes were seeded on the top of those hydrogels to develop a vascularized dermo-epidermal skin substitute.; Flow cytometric analysis of surface markers of the freshly isolated SVF showed the expression of endothelial markers (CD31, CD34, CD146), mesenchymal/stromal cell-associated markers (CD44, CD73, CD90, CD105), stem cell markers (CD49f, CD117, CD133), and additionally hematopoietic markers (CD14, CD15, CD45). Further analysis of white adipose-derived endothelial cells (watECs) revealed the co-expression of CD31, CD34, CD90, CD105, and partially CD146 on these cells. WatECs were separated from adipose-stromal cells (watASCs) using FACS sorting. WatASCs and watECs cultured separately in a 3D hydrogel for 3 weeks did not form any vascular structures. Only if co-cultured, both cell types aligned to develop a ramified vascular network in vitro with continuous endothelial lumen formation. Transplantation of those 3D-hydrogels onto immuno-incompetent rats resulted in a rapid connection of human capillaries with the host vessels and formation of functional, blood-perfused mosaic human-rat vessels within only 3-4 days.; Adipose tissue represents an attractive cell source due to the ease of isolation and abundance of endothelial as well as mesenchymal cell lineages. Adipose-derived SVF cells exhibit the ability to form microvascular structures in vitro and support the accelerated blood perfusion in skin substitutes in vivo when transplanted.
Faculties and Departments:03 Faculty of Medicine
UniBasel Contributors:Scherberich, Arnaud and Martin, Ivan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer Verlag
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Oct 2017 09:00
Deposited On:09 Oct 2017 09:00

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