title: Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume.
abstract: Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.
authors.affiliation: UMC Utrecht, Dept. Orthopaedics, Heidelberglaan 100, 3584 CX Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.j.alblas@umcutrecht.nl.
authors.forename: F
authors.initials: F
authors.lastname: Wegman
authors.forename: M T
authors.initials: MT
authors.lastname: Poldervaart
authors.forename: Y J
authors.initials: YJ
authors.lastname: van der Helm
authors.forename: F C
authors.initials: FC
authors.lastname: Oner
authors.forename: W J
authors.initials: WJ
authors.lastname: Dhert
authors.forename: J
authors.initials: J
authors.lastname: Alblas
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D006041:Goats; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010957:Plasmids / Q000235:genetics
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D004247:DNA