Home About us Contact
|
Home About us Contact | ||
|
|
||
Human Bone Morphogenetic Protein (human + bone_morphogenetic_protein)
Selected AbstractsEarly osteoblastic differentiation induced by dexamethasone enhances adenoviral gene delivery to marrow stromal cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2004Jeremy S. Blum Abstract We investigated the implications of induced osteogenic differentiation on gene delivery in multipotent rat marrow stromal cells (MSCs). Prior to genetic manipulation cells were cultured with or without osteogenic supplements (5 ± 10,8 M dexamethasone, 160 ,M l-ascorbic acid 2-phosphate, and 10 mM ,-glycerophosphate). Comparison of liposome, retroviral, and adenoviral vectors demonstrated that all three vectors could mediate gene delivery to primary rat MSCs. When these vectors were applied in the absence or presence of osteogenic supplements, we found that MSCs differentiated prior to transduction with adenovirus type 5 vectors produced a 300% increase in transgene expression compared to MSCs that were not exposed to osteogenic supplements. This differentiation effect appeared specific to adenoviral mediated gene delivery, since there was minimal increase in retroviral gene delivery and no increase in liposome gene delivery when MSCs were treated with osteogenic supplements. In addition, we also determined this increase in transgene production to occur at a higher concentration of dexamethasone (5 ± 10,8 M) in the culture medium of MSCs prior to adenoviral transduction. We found that this increased transgene production could be extended to the osteogenic protein, human bone morphogenetic protein 2 (hBMP-2). When delivered by an adenoviral vector, hBMP-2 transgene production could be increased from 1.4 ng/105 cells/3 days to 4.3 ng/105 cells/3 days by culture of MSCs with osteogenic supplements prior to transduction. These results indicate that the utility of MSCs as a therapeutic protein delivery mechanism through genetic manipulation can be enhanced by pre-culture of these cells with dexamethasone. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in miceTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Xiao S. Zhang Abstract Background Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV-based retroviral vector to express human bone morphogenetic protein 4 (BMP4). Methods We assessed two approaches for administering transduced MSCs. ,-Galactosidase (,-Gal) transduced C57BL/6J mouse MSCs were injected intravenously via tail vein or directly injected into the femoral bone marrow cavity of non-marrow-ablated syngenic recipient mice and bone marrow cavity engraftment was assessed. BMP4- or ,-Gal-transduced cells were injected into the femoral bone marrow cavity and effects on bone were evaluated by X-ray, peripheral quantitative computed tomography (pQCT), and histology. Results After tail-vein injection less than 20% of recipient mice contained ,-Gal-positive donor cells in femur, humerus or vertebra marrow cavities combined, and in these mice only 0.02,0.29% of injected cells were present in the bone marrow. In contrast, direct intramedullary injection was always successful and an average of 2% of injected cells were present in the injected femur marrow cavity 24 hours after injection. Numbers of donor cells decreased over the next 14 days. Intramedullary injection of BMP4-transduced MSCs induced bone formation. Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14 days and total BMD increased 6.5% at 14 days and 10.4% at 56 days. Conclusions The present findings support the feasibility of using ex vivo MSC-based retroviral gene therapy to induce relatively sustained new bone formation, with normal histological appearance, at endosteal bone sites. Copyright © 2004 John Wiley & Sons, Ltd. [source] rhBMP-2/,BSM® Induces Significant Vertical Alveolar Ridge Augmentation and Dental Implant OsseointegrationCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 4 2002Ulf M.E. Wikesjö DDS ABSTRACT Background: Recombinant human bone morphogenetic protein 2 (rhBMP-2) in a carrier has been shown to induce significant bone formation. Several candidate carriers, however, lack structural integrity to offset compressive forces that may compromise rhBMP-2 bone induction, in particular, for challenging onlay indications such as alveolar ridge augmentation. Purpose: The objective of this study was to evaluate rhBMP-2 in a calcium-phosphate cement carrier, ,BSM, for vertical alveolar ridge augmentation and immediate dental implant Osseointegration. Materials and Methods: Six adult Hound Labrador mongrels with 5 mm critical size supra-alveolar peri-implant defects were used. Three animals received rhBMP-2/,BSM (rhBMP-2 at 0.40 and 0.75 mg/mL) in contralateral jaw quadrants (total implant volume/defect , 1.5 mL). Three animals received ,BSM without rhBMP-2 (control group). The animals were euthanized at 16 weeks post surgery, and block biopsies were processed for histologie and histometric analysis. Results: rhBMP-2/,BSM induced substantial augmentation of the alveolar ridge. Control sites exhibited limited new bone formation. Vertical bone augmentation averaged (SD) 4.9 ± 1.0 mm (rhBMP-2 at 0.40 mg/mL), 5.3 ± 0.3 mm (rhBMP-2 at 0.75 mg/mL), and 0.4 ± 0.4 mm (control); new bone area 8.5 ± 4.2 mm 2, 9.0 ± 1.9 mm 2, and 0.5 ± 0.4 mm 2; new bone density 55.1 ± 6.4%, 61.1 ± 6.0%, and 67.7 ± 9.5%; and new bone-implant contact 26.9 ± 17.5%, 28.5 ± 1.4%, and 24.6 ± 16.1%, respectively. Residual ,BSM comprised 1% of the new bone. Bone density for the contiguous resident bone ranged from 65 to 71%, and bone-implant contact ranged from 49 to 64%. Conclusions: Surgical implantation of rhBMP-2/,BSM appears an effective protocol for vertical alveolar ridge augmentation procedures and immediate dental implant Osseointegration and for onlay indications of lesser complexity. [source] Bone Marrow Mesenchymal Stem Cells Form Ectopic Woven Bone In Vivo Through Endochondral Bone FormationARTIFICIAL ORGANS, Issue 4 2009Sophia Chia-Ning Chang Abstract:, Autologous vascularized bone grafts, allografts, and biocompatible artificial bone substitutes each have their shortcomings. Bones regenerated using recombinant human bone morphogenetic proteins, demineralized bone powder, or combinations of these are generally small and do not meet the need. The current trend is to use tissue engineering approaches with bone marrow mesenchymal stem cells (MSCs) to generate bones of a desired size and shape. A suspension of osteogenically induced MSCs (CD11a,, CD29+, CD44+) was added to 2% alginate, gelled by mixing this combination with calcium sulfate (CaSO4 0.2 g/mL), and injected into the subcutaneous pocket in the dorsal aspect of nude mice. Cells of various concentrations (0, 10, 50, and 70 million/mL) were used. These implanted constructs were harvested at predetermined times up to 30 weeks for histology. The doubling time of bovine MSCs is 3.75 ± 1.96 days and the proliferation is rapid. Histological evaluation revealed signs of endochondrosis with woven bone deposition. The equilibrium modulus increased with time in vivo, though less than that of normal tissue. Implants seeded with 70 million cells/mL for 6 months resulted in the best formation of equilibrium modulus. This approach has several advantages: (i) obtaining MSCs is associated with low donor morbidity; (ii) MSCs proliferate rapidly in vitro, and a large number of viable cells can be obtained; and (iii) the MSC/alginate constructs can develop into bone-like nodules with high cell viability. Such a system may be useful in large-scale production of bony implants or in the repair of bony defects. The fact that endochondral bone formation led to woven bone suggests its potential feasibility in regional cell therapy. [source] | |||||||||||||