title: Cell interactions between human progenitor-derived endothelial cells and human mesenchymal stem cells in a three-dimensional macroporous polysaccharide-based scaffold promote osteogenesis.
abstract: Several studies have reported the benefits of mesenchymal stem cells (MSCs) for bone tissue engineering. However, vascularization remains one of the main obstacles that must be overcome to reconstruct large bone defects. In vitro prevascularization of the three-dimensional (3-D) constructs using co-cultures of human progenitor-derived endothelial cells (PDECs) with human bone marrow mesenchymal stem cells (HBMSCs) appeared as a potential strategy. However, the crosstalk between the two lineages has been studied in two-dimensional (2-D), but remains unknown in 3-D. The aim of this study is to investigate the cell interactions between PDECs and HBMSCs in a porous matrix composed of polysaccharides. This biodegradable scaffold promotes cell interactions by inducing multicellular aggregates composed of HBMSCs surrounded by PDECs. Cell aggregation contributes to the formation of junctional proteins composed of Connexin43 (Cx43) and VE-cadherin, and an activation of osteoblastic differentiation of HBMSCs stimulated by the presence of PDECs. Inhibition of Cx43 by mimetic peptide 43GAP27 induced a decrease in mRNA levels of Cx43 and all the bone-specific markers. Finally, subcutaneous implantations for 3 and 8 weeks in NOG mice revealed an increase in osteoid formation with the tissue-engineered constructs seeded with HBMSCs/PDECs compared with those loaded with HBMSCs alone. Taking together, these results demonstrate that this 3-D microenvironment favored cell communication, osteogenesis and bone formation.
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France. julien.guerrero@inserm.fr
authors.forename: J
authors.initials: J
authors.lastname: Guerrero
authors.forename: S
authors.initials: S
authors.lastname: Catros
authors.forename: S-M
authors.initials: SM
authors.lastname: Derkaoui
authors.forename: C
authors.initials: C
authors.lastname: Lalande
authors.forename: R
authors.initials: R
authors.lastname: Siadous
authors.forename: R
authors.initials: R
authors.lastname: Bareille
authors.forename: N
authors.initials: N
authors.lastname: Thébaud
authors.forename: L
authors.initials: L
authors.lastname: Bordenave
authors.forename: O
authors.initials: O
authors.lastname: Chassande
authors.forename: C
authors.initials: C
authors.lastname: Le Visage
authors.forename: D
authors.initials: D
authors.lastname: Letourneur
authors.forename: J
authors.initials: J
authors.lastname: Amédée
mesh_terms: D002450:Cell Communication / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D011134:Polysaccharides / Q000737:chemistry*; D016062:Porosity; D054457:Tissue Scaffolds
chemical_list: D011134:Polysaccharides
keywords: Co-culture; Differentiation; Endothelial cells; Mesenchymal stem cells; Tissue Regeneration