title: Adenoviral BMP-2 gene transfer in mesenchymal stem cells: in vitro and in vivo bone formation on biodegradable polymer scaffolds.
abstract: The aim of this study was to determine the feasibility of adenoviral gene transfer into primary human bone marrow osteoprogenitor cells in combination with biodegradeable scaffolds to tissue-engineer bone. Osteoprogenitors were infected with AxCAOBMP-2, a vector carrying the human BMP-2 gene. Alkaline phosphatase activity was induced in C2C12 cells following culture with conditioned media from BMP-2 expressing cells, confirming successful secretion of active BMP-2. Expression of alkaline phosphatase activity, type I collagen and mineralisation confirmed bone cell differentiation and maintenance of the osteoblast phenotype in extended culture for up to 6 weeks on PLGA porous scaffolds. In vivo implantation of adenoviral osteoprogenitor constructs on PLGA biodegradeable scaffolds, using diffusion chambers, also demonstrated bone cell differentiation and production of bone tissue. The maintenance of the osteoblast phenotype in extended culture and generation of mineralised 3-D scaffolds containing such constructs indicate the potential of such bone tissue engineering approaches in bone repair.
authors.affiliation: University Orthopaedics, University of Southampton, General Hospital, Southampton SO16 6YD, United Kingdom.
authors.forename: Kris
authors.initials: K
authors.lastname: Partridge
authors.forename: Xuebin
authors.initials: X
authors.lastname: Yang
authors.forename: Nicholas M P
authors.initials: NM
authors.lastname: Clarke
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okubo
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Bessho
authors.forename: Walter
authors.initials: W
authors.lastname: Sebald
authors.forename: Steven M
authors.initials: SM
authors.lastname: Howdle
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
mesh_terms: D020341:Absorbable Implants; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D005240:Feasibility Studies; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000821:virology; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D023822:Tissue Engineering / Q000379:methods*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid