title: BMP-2-transduced human bone marrow stem cells enhance neo-bone formation in a rat critical-sized femur defect.
abstract: Synthetic graft materials are considered as possible substitutes for cancellous bone, but lack osteogenic and osteoinductive properties. In this study, we investigated how composite scaffolds of βTCP containing osteogenic human bone marrow mesenchymal stem cells (hBMSCs) and osteoinductive bone morphogenetic protein-2 (BMP-2) influenced the process of fracture healing. hBMSCs were loaded into βTCP scaffolds 24 h before implantation in a rat critical-sized bone defect. hBMSCs were either stimulated with rhBMP-2 or transduced with BMP-2 by gene transfer. The effect of both protein stimulation and gene transfer was compared for osteogenic outcome. X-rays were conducted at weeks 0, 1, 3, 6, 9 and 12 post-operatively. In addition, bone-labelling fluorochromes were applied at 0, 3, 6 and 9 weeks. Histological analysis was performed for the amount of callus tissue and cartilage formation. At 6 weeks, the critical-sized defect in 33% of the rats treated with the Ad-BMP-2-transduced hBMSCs/βTCP scaffolds was radiographically bridged. In contrast, in only 10% of the rats treated with rhBMP2/hBMSCs, 12 weeks post-treatment, the bone defect was closed in all treated rats of the Ad-BMP-2 group except for one. Histology showed significantly higher amounts of callus formation in both Ad-BMP-2- and rhBMP-2-treated rats. The amount of neocartilage was less pronounced in both BMP-2-related groups. In summary, scaffolds with BMP-2-transduced hBMSCs performed better than those with the rhBMP2/hBMSCs protein. These results suggest that combinations of osteoconductive biomaterials with genetically modified MSCs capable of secreting osteoinductive proteins may represent a promising alternative for bone regeneration. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Trauma Department, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Müller
authors.affiliation: Trauma Department, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Hildebrandt
authors.affiliation: Department of Trauma Surgery, Centre Hospitalier de Luxembourg (CHL), Luxembourg.
authors.forename: Torsten
authors.initials: T
authors.lastname: Gerich
authors.affiliation: Trauma Department, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Krettek
authors.affiliation: Department of Experimental Trauma Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany.
authors.forename: Martijn
authors.identifier: 0000-0001-5104-9881
authors.initials: M
authors.lastname: van Griensven
authors.affiliation: Department of Experimental Trauma Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany.
authors.forename: Elizabeth
authors.identifier: 0000-0002-0484-4847
authors.initials: E
authors.lastname: Rosado Balmayor
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D002130:Calcium Phosphates / Q000494:pharmacology; D005269:Femur / Q000187:drug effects / Q000473:pathology*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D011923:Rats, Nude; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects; D055815:Young Adult
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C018392:tricalcium phosphate
keywords: adenovirus; bone marrow stem cells; bone morphogenetic protein 2; femur critical-sized bone defect; gene transfer; rat