title: Bone grafts engineered from human adipose-derived stem cells in dynamic 3D-environments.
abstract: Modular tissue engineering (TE) is a promising alternative to overcome the limits in traditional TE. In the present study, adipose tissue derived stem cells (ADSC)-laden microcarriers are used as building blocks (microtissues) that self-assemble into macrotissues in a bottom-up approach. These bone grafts were compared with a classical top-down approach (scaffolds). This concept was compared with bone marrow derived stem cells (BMSC) as cell source. Cells were immunophenotypically analyzed, followed by 2D/3D osteogenic differentiation in static/dynamic conditions. The bone graft quality was evaluated by (immuno)histochemistry and gene expression. After 6 weeks of dynamic culturing, scaffolds were highly colonized although not in the center and the osteogenic gene expression was higher in contrast to static cultures. A cell-to-microcarrier ratio of 5 × 10(6) cells-0.09 g microcarriers leaded to aggregate formation resulting in microtissues with subsequent macrotissue formation. ADSC/BMSC on scaffolds showed a downregulation of Runx2 and collagen I, demonstrating the end-stage, in contrary to microcarriers, where an upregulation of Runx2, collagen I together with BSP and osteocalcin was observed. This paper showed that high quality bone grafts (2 cm³) can be engineered in a bottom-up approach with cell-laden microcarriers.
authors.affiliation: Tissue Engineering Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (6B3), 9000 Ghent, Belgium.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Declercq
authors.forename: Tamara
authors.initials: T
authors.lastname: De Caluwé
authors.forename: Olga
authors.initials: O
authors.lastname: Krysko
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Cornelissen
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D019149:Bioreactors; D016025:Bone Transplantation / Q000379:methods / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D010012:Osteogenesis / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds