title: Adipose stromal cell tubule network model provides a versatile tool for vascular research and tissue engineering.
abstract: The current limitation in designing three-dimensional tissue models is the lack of adequate vascularization with mature and stable vessels. Adipose tissue is known to secrete several angiogenic factors, and human adipose stromal cells (hASC) are known to promote vessel growth, maturation and stabilization. In this study, hASC were induced to angiogenesis with growth factor-enriched medium either in monoculture or in coculture with human umbilical vein endothelial cells (HUVEC) and analyzed for vascular, pericytic and smooth muscle cell markers. hASC and HUVEC cocultures showed an accelerated proliferation rate and the cells self-assembled, independent of the cell passage number, into multilayered three-dimensional tubular networks. The networks of hASC and HUVEC expressed endothelial markers, a complete basement membrane and vessel-supporting cells with contractile properties. A hASC and green fluorescence protein-HUVEC-infection model revealed that cocultures consisted of a mosaic of von Willebrand factor-positive cells derived from both cell populations - hASC and HUVEC. hASC monoculture had passage- and donor-dependent ability to form tubular networks, with half of the cultures presenting tubule structures and basement membrane formation. Pericytic and smooth muscle cell markers were expressed in hASC monoculture even when tubules were absent. By combining the potential properties of hASC and features from the present angiogenesis assays, we generated a natural-like, xeno-free, prevascular-like network in vitro model with excellent reproducibility and minimal limitations in technical performance. This tubular network model is an excellent tool for studying cell interactions during vascular development, for chemical and drug testing and for developing natural-like, multilayered, vascularized, scaffold-free tissue models.
authors: Department of Cell Biology, Finnish Center for Alternative Methods, School of Medicine, University of Tampere, Tampere, Finland. riina.sarkanen@uta.fi
authors: Jertta-Riina
authors: JR
authors: Sarkanen
authors: Hanna
authors: H
authors: Vuorenpää
authors: Outi
authors: O
authors: Huttala
authors: Bettina
authors: B
authors: Mannerström
authors: Hannu
authors: H
authors: Kuokkanen
authors: Susanna
authors: S
authors: Miettinen
authors: Tuula
authors: T
authors: Heinonen
authors: Timo
authors: T
authors: Ylikomi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*