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dc.contributor.authorPedersen, Torbjørn Østviken_US
dc.contributor.authorBlois, Anna Len_US
dc.contributor.authorXing, Zheen_US
dc.contributor.authorXue, Yingen_US
dc.contributor.authorSun, Yangen_US
dc.contributor.authorFinne-Wistrand, Annaen_US
dc.contributor.authorAkslen, Lars A.en_US
dc.contributor.authorLorens, James B.en_US
dc.contributor.authorLeknes, Knut N.en_US
dc.contributor.authorFristad, Ingeen_US
dc.contributor.authorMustafa, Kamal Babikeir Elnen_US
dc.description.abstractIntroduction: A major determinant of the potential size of cell/scaffold constructs in tissue engineering is vascularization. The aims of this study were twofold: first to determine the in vitro angiogenic and osteogenic gene- expression profiles of endothelial cells (ECs) and mesenchymal stem cells (MSCs) cocultured in a dynamic 3D environment; and second, to assess differentiation and the potential for osteogenesis after in vivo implantation. Methods: MSCs and ECs were grown in dynamic culture in poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) copolymer scaffolds for 1 week, to generate three-dimensional endothelial microvascular networks. The constructs were then implanted in vivo, in a murine model for ectopic bone formation. Expression of selected genes for angiogenesis and osteogenesis was studied after a 1-week culture in vitro. Human cell proliferation was assessed as expression of ki67, whereas α-smooth muscle actin was used to determine the perivascular differentiation of MSCs. Osteogenesis was evaluated in vivo through detection of selected markers, by using real-time RT-PCR, alkaline phosphatase (ALP), Alizarin Red, hematoxylin/eosin (HE), and Masson trichrome staining. Results: The results show that endothelial microvascular networks could be generated in a poly(LLA-co-DXO) scaffold in vitro and sustained after in vivo implantation. The addition of ECs to MSCs influenced both angiogenic and osteogenic gene-expression profiles. Furthermore, human ki67 was upregulated before and after implantation. MSCs could support functional blood vessels as perivascular cells independent of implanted ECs. In addition, the expression of ALP was upregulated in the presence of endothelial microvascular networks. Conclusions: This study demonstrates that copolymer poly(LLA-co-DXO) scaffolds can be prevascularized with ECs and MSCs. Although a local osteoinductive environment is required to achieve ectopic bone formation, seeding of MSCs with or without ECs increases the osteogenic potential of tissue-engineered constructs.en_US
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.subjectTissue engineeringeng
dc.subjectEndothelial cellseng
dc.subjectMesenchymal stem cellseng
dc.titleEndothelial microvascular networks affect gene-expression profiles and osteogenic potential of tissue-engineered constructsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderTorbjorn O Pedersen et al.; licensee BioMed Central Ltd.
dc.rights.holderCopyright 2013 Pedersen et al.; licensee BioMed Central Ltd.
dc.source.journalStem Cell Research & Therapy

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