title: The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.
abstract: Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.
authors.affiliation: 1 Inserm, U1026, Tissue Bioengineering, University of Bordeaux , Bordeaux, France .
authors.forename: Julien
authors.initials: J
authors.lastname: Guerrero
authors.forename: Hugo
authors.initials: H
authors.lastname: Oliveira
authors.forename: Sylvain
authors.initials: S
authors.lastname: Catros
authors.forename: Robin
authors.initials: R
authors.lastname: Siadous
authors.forename: Sidi-Mohammed
authors.initials: SM
authors.lastname: Derkaoui
authors.forename: Reine
authors.initials: R
authors.lastname: Bareille
authors.forename: Didier
authors.initials: D
authors.lastname: Letourneur
authors.forename: Joëlle
authors.initials: J
authors.lastname: Amédée
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D001842:Bone and Bones / Q000502:physiology*; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D055806:Microvessels / Q000166:cytology; D018919:Neovascularization, Physiologic; D009928:Organ Specificity; D010012:Osteogenesis; D016062:Porosity; D019919:Prosthesis Implantation; D018874:Spheroids, Cellular / Q000166:cytology; D040521:Subcutaneous Tissue; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D015415:Biomarkers; D018031:Connexin 43