Dermal fibroblast‐mediated BMP2 therapy to accelerate bone healing in an equine osteotomy model
Identifieur interne : 003092 ( Main/Exploration ); précédent : 003091; suivant : 003093Dermal fibroblast‐mediated BMP2 therapy to accelerate bone healing in an equine osteotomy model
Auteurs : Akikazu Ishihara [États-Unis] ; Lisa J. Zekas [États-Unis] ; Alan S. Litsky [États-Unis] ; Steven E. Weisbrode [États-Unis] ; Alicia L. Bertone [États-Unis]Source :
- Journal of Orthopaedic Research [ 0736-0266 ] ; 2010-03.
English descriptors
- Teeft :
- Adenoviral, Adenoviral vectors, Adenoviral vectors encoding, Autologous, Autologous cells, Biomechanical testing, Biopsy, Bmp2, Bmp2 gene, Bmp2 gene augmentation, Bmp2 gene transduction, Bmp2 protein production, Bmp2 therapy, Bone, Bone defects, Bone formation, Bone healing, Bone healing site, Bone miner, Bone regeneration, Bone specimens, Bone volume, Bony mineralization, Broblasts, Brous tissue, Callus, Cartilage, Cartilage formation, Cell injection, Chondrogenic differentiation, Cubic volume, Data comparison, Defect, Dfbs, Direct gene delivery, Endochondral, Equine, External callus, Fracture, Future study, Gbss, Gbss group, Gbss injections, Gbsstreated defects, Gene, Gene expression, Gene therapy, Gene transduction, General anesthesia, Greater amount, Greater area, Greater bone formation, Greater composition, Greater formation, Greater size, Greater strength, Healing, High numbers, Histologic evaluation, Implantation, Large animal model, Mature cartilage, Mechanical strength, Mechanical testing, Mineral density, Mineral deposition, Mineralization, Mineralization activity, Mineralized callus, Nodular bone formation, Normality tests, Ohio state university, Open tibial fractures, Orthopaedic, Orthopaedic research march, Orthopaedic research society, Osseous tissue, Osteoclast formation, Osteogenic, Osteogenic differentiation, Osteogenic gene, Osteoprogenitor cells, Osteotomy, Osteotomy edge, Osteotomy edges, Osteotomy gaps, Osteotomy healing, Osteotomy site, Other treatments, Paracrine effect, Percutaneous, Percutaneous injection, Proc natl acad, Radiographic evaluation, Repair site, Saline control, Secrete bmp2, Skin biopsy, Skin punch biopsy, Stiffness, Supplemental table, Surgical procedure, Time point, Torsional, Torsional stiffness, Total volume, Transduction, Transplantation, Treatment groups, Wiley periodicals.
Abstract
This study evaluated healing of equine metacarpal/metatarsal osteotomies in response to percutaneous injection of autologous dermal fibroblasts (DFbs) genetically engineered to secrete bone morphogenetic protein‐2 (BMP2) or demonstrate green fluorescent protein (GFP) gene expression administered 14 days after surgery. Radiographic assessment of bone formation indicated greater and earlier healing of bone defects treated with DFb with BMP2 gene augmentation. Quantitative computed tomography and biomechanical testing revealed greater mineralized callus and torsional strength of DFb‐BMP2‐treated bone defects. On the histologic evaluation, the bone defects with DFb‐BMP2 implantation had greater formation of mature cartilage and bone nodules within the osteotomy gap and greater mineralization activity on osteotomy edges. Autologous DFbs were successfully isolated in high numbers by a skin biopsy, rapidly expanded without fastidious culture techniques, permissive to adenoviral vectors, and efficient at in vitro BMP2 protein production and BMP2‐induced osteogenic differentiation. This study demonstrated an efficacy and feasibility of DFb‐mediated BMP2 therapy to accelerate the healing of osteotomies. Skin cell‐mediated BMP2 therapy may be considered as a potential treatment for various types of fractures and bone defects. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:403–411, 2010
Url:
DOI: 10.1002/jor.20978
Affiliations:
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xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Correspondence address: Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Orthopaedic Research</title><title level="j" type="alt">JOURNAL OF ORTHOPAEDIC RESEARCH</title><idno type="ISSN">0736-0266</idno><idno type="eISSN">1554-527X</idno><imprint><biblScope unit="vol">28</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="403">403</biblScope><biblScope unit="page" to="411">411</biblScope><biblScope unit="page-count">9</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-03">2010-03</date></imprint><idno type="ISSN">0736-0266</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0736-0266</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Adenoviral</term><term>Adenoviral vectors</term><term>Adenoviral vectors encoding</term><term>Autologous</term><term>Autologous cells</term><term>Biomechanical testing</term><term>Biopsy</term><term>Bmp2</term><term>Bmp2 gene</term><term>Bmp2 gene augmentation</term><term>Bmp2 gene transduction</term><term>Bmp2 protein production</term><term>Bmp2 therapy</term><term>Bone</term><term>Bone defects</term><term>Bone formation</term><term>Bone healing</term><term>Bone healing site</term><term>Bone miner</term><term>Bone regeneration</term><term>Bone specimens</term><term>Bone volume</term><term>Bony mineralization</term><term>Broblasts</term><term>Brous tissue</term><term>Callus</term><term>Cartilage</term><term>Cartilage formation</term><term>Cell injection</term><term>Chondrogenic differentiation</term><term>Cubic volume</term><term>Data comparison</term><term>Defect</term><term>Dfbs</term><term>Direct gene delivery</term><term>Endochondral</term><term>Equine</term><term>External callus</term><term>Fracture</term><term>Future study</term><term>Gbss</term><term>Gbss group</term><term>Gbss injections</term><term>Gbsstreated defects</term><term>Gene</term><term>Gene expression</term><term>Gene therapy</term><term>Gene transduction</term><term>General anesthesia</term><term>Greater amount</term><term>Greater area</term><term>Greater bone formation</term><term>Greater composition</term><term>Greater formation</term><term>Greater size</term><term>Greater strength</term><term>Healing</term><term>High numbers</term><term>Histologic evaluation</term><term>Implantation</term><term>Large animal model</term><term>Mature cartilage</term><term>Mechanical strength</term><term>Mechanical testing</term><term>Mineral density</term><term>Mineral deposition</term><term>Mineralization</term><term>Mineralization activity</term><term>Mineralized callus</term><term>Nodular bone formation</term><term>Normality tests</term><term>Ohio state university</term><term>Open tibial fractures</term><term>Orthopaedic</term><term>Orthopaedic research march</term><term>Orthopaedic research society</term><term>Osseous tissue</term><term>Osteoclast formation</term><term>Osteogenic</term><term>Osteogenic differentiation</term><term>Osteogenic gene</term><term>Osteoprogenitor cells</term><term>Osteotomy</term><term>Osteotomy edge</term><term>Osteotomy edges</term><term>Osteotomy gaps</term><term>Osteotomy healing</term><term>Osteotomy site</term><term>Other treatments</term><term>Paracrine effect</term><term>Percutaneous</term><term>Percutaneous injection</term><term>Proc natl acad</term><term>Radiographic evaluation</term><term>Repair site</term><term>Saline control</term><term>Secrete bmp2</term><term>Skin biopsy</term><term>Skin punch biopsy</term><term>Stiffness</term><term>Supplemental table</term><term>Surgical procedure</term><term>Time point</term><term>Torsional</term><term>Torsional stiffness</term><term>Total volume</term><term>Transduction</term><term>Transplantation</term><term>Treatment groups</term><term>Wiley periodicals</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This study evaluated healing of equine metacarpal/metatarsal osteotomies in response to percutaneous injection of autologous dermal fibroblasts (DFbs) genetically engineered to secrete bone morphogenetic protein‐2 (BMP2) or demonstrate green fluorescent protein (GFP) gene expression administered 14 days after surgery. Radiographic assessment of bone formation indicated greater and earlier healing of bone defects treated with DFb with BMP2 gene augmentation. Quantitative computed tomography and biomechanical testing revealed greater mineralized callus and torsional strength of DFb‐BMP2‐treated bone defects. On the histologic evaluation, the bone defects with DFb‐BMP2 implantation had greater formation of mature cartilage and bone nodules within the osteotomy gap and greater mineralization activity on osteotomy edges. Autologous DFbs were successfully isolated in high numbers by a skin biopsy, rapidly expanded without fastidious culture techniques, permissive to adenoviral vectors, and efficient at in vitro BMP2 protein production and BMP2‐induced osteogenic differentiation. This study demonstrated an efficacy and feasibility of DFb‐mediated BMP2 therapy to accelerate the healing of osteotomies. Skin cell‐mediated BMP2 therapy may be considered as a potential treatment for various types of fractures and bone defects. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:403–411, 2010</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Ishihara, Akikazu" sort="Ishihara, Akikazu" uniqKey="Ishihara A" first="Akikazu" last="Ishihara">Akikazu Ishihara</name></region><name sortKey="Bertone, Alicia L" sort="Bertone, Alicia L" uniqKey="Bertone A" first="Alicia L." last="Bertone">Alicia L. Bertone</name><name sortKey="Bertone, Alicia L" sort="Bertone, Alicia L" uniqKey="Bertone A" first="Alicia L." last="Bertone">Alicia L. Bertone</name><name sortKey="Bertone, Alicia L" sort="Bertone, Alicia L" uniqKey="Bertone A" first="Alicia L." last="Bertone">Alicia L. Bertone</name><name sortKey="Bertone, Alicia L" sort="Bertone, Alicia L" uniqKey="Bertone A" first="Alicia L." last="Bertone">Alicia L. Bertone</name><name sortKey="Bertone, Alicia L" sort="Bertone, Alicia L" uniqKey="Bertone A" first="Alicia L." last="Bertone">Alicia L. Bertone</name><name sortKey="Ishihara, Akikazu" sort="Ishihara, Akikazu" uniqKey="Ishihara A" first="Akikazu" last="Ishihara">Akikazu Ishihara</name><name sortKey="Litsky, Alan S" sort="Litsky, Alan S" uniqKey="Litsky A" first="Alan S." last="Litsky">Alan S. Litsky</name><name sortKey="Weisbrode, Steven E" sort="Weisbrode, Steven E" uniqKey="Weisbrode S" first="Steven E." last="Weisbrode">Steven E. Weisbrode</name><name sortKey="Zekas, Lisa J" sort="Zekas, Lisa J" uniqKey="Zekas L" first="Lisa J." last="Zekas">Lisa J. Zekas</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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