Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects
The direct, local, administration of adenovirus carrying human BMP-2 cDNA (Ad.BMP-2) heals critical-sized femoral bone defects in rabbit and rat models. However, the outcome is suboptimal and the technology needs to provide a more reliable and uniform outcome. To this end, we investigated whether th...
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| Veröffentlicht in: | Gene therapy 2007-07, Vol.14 (13), p.1039-1044 |
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| creator | Betz, O B Betz, V M Nazarian, A Egermann, M Gerstenfeld, L C Einhorn, T A Vrahas, M S Bouxsein, M L Evans, C H |
| description | The direct, local, administration of adenovirus carrying human BMP-2 cDNA (Ad.BMP-2) heals critical-sized femoral bone defects in rabbit and rat models. However, the outcome is suboptimal and the technology needs to provide a more reliable and uniform outcome. To this end, we investigated whether the timing of Ad.BMP-2 administration influenced the formation of mineralized tissue within the defect. Critical-sized defects were created in the femora of 28 Sprague–Dawley rats. Animals were injected intralesionally with a single, percutaneous injection of Ad.BMP-2 (4 × 10
8
plaque-forming units) either intraoperatively (day 0) or 24 h (day 1), 5 days or 10 days after surgery. The femora were evaluated 8 weeks after surgery by X-ray, microcomputed tomography, dual-energy X-ray absorptiometry and biomechanical testing. The incidence of radiological union was markedly increased when administration of Ad.BMP-2 was delayed until days 5 and 10, at which point 86% of the defects healed. These time points also provided greater bone mineral content within the defect site and improved the average mechanical strength of the healed bone. Thus, delaying the injection of Ad.BMP-2 until 5 or 10 days after surgery enables a greater percentage of critical-sized, segmental defects to achieve radiological union, producing a repair tissue with enhanced mineralization and greater mechanical strength. |
| doi_str_mv | 10.1038/sj.gt.3302956 |
| format | Article |
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8
plaque-forming units) either intraoperatively (day 0) or 24 h (day 1), 5 days or 10 days after surgery. The femora were evaluated 8 weeks after surgery by X-ray, microcomputed tomography, dual-energy X-ray absorptiometry and biomechanical testing. The incidence of radiological union was markedly increased when administration of Ad.BMP-2 was delayed until days 5 and 10, at which point 86% of the defects healed. These time points also provided greater bone mineral content within the defect site and improved the average mechanical strength of the healed bone. Thus, delaying the injection of Ad.BMP-2 until 5 or 10 days after surgery enables a greater percentage of critical-sized, segmental defects to achieve radiological union, producing a repair tissue with enhanced mineralization and greater mechanical strength.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302956</identifier><identifier>PMID: 17460719</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Adenoviruses ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animal models ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Bone and Bones - metabolism ; Bone and Bones - pathology ; Bone diseases ; Bone growth ; Bone mineral content ; Bone Morphogenetic Protein 2 ; Bone morphogenetic proteins ; Bone Morphogenetic Proteins - genetics ; Bone Morphogenetic Proteins - metabolism ; Bone Regeneration ; Bone surgery ; Bones ; Care and treatment ; Cell Biology ; Computed tomography ; Dual energy X-ray absorptiometry ; Fracture Fixation - methods ; Fracture Healing ; Fractures, Bone - metabolism ; Fractures, Bone - pathology ; Fractures, Bone - therapy ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Genetic aspects ; Genetic Therapy - methods ; Genetic vectors ; Genetic Vectors - administration & dosage ; Health. Pharmaceutical industry ; Human Genetics ; Industrial applications and implications. Economical aspects ; Injection ; Male ; Mechanical properties ; Medical sciences ; Mineralization ; Models, Animal ; Nanotechnology ; original-article ; Physiological aspects ; Proteins ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Rodents ; Surgery ; Transduction, Genetic - methods ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - metabolism ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Gene therapy, 2007-07, Vol.14 (13), p.1039-1044</ispartof><rights>Springer Nature Limited 2007</rights><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2007</rights><rights>Nature Publishing Group 2007.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c644t-37ddcc0b657b7bf71f9de3bf78b9921e555025528500ac603a127123c5d196d73</citedby><cites>FETCH-LOGICAL-c644t-37ddcc0b657b7bf71f9de3bf78b9921e555025528500ac603a127123c5d196d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.gt.3302956$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gt.3302956$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18835105$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17460719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Betz, O B</creatorcontrib><creatorcontrib>Betz, V M</creatorcontrib><creatorcontrib>Nazarian, A</creatorcontrib><creatorcontrib>Egermann, M</creatorcontrib><creatorcontrib>Gerstenfeld, L C</creatorcontrib><creatorcontrib>Einhorn, T A</creatorcontrib><creatorcontrib>Vrahas, M S</creatorcontrib><creatorcontrib>Bouxsein, M L</creatorcontrib><creatorcontrib>Evans, C H</creatorcontrib><title>Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>The direct, local, administration of adenovirus carrying human BMP-2 cDNA (Ad.BMP-2) heals critical-sized femoral bone defects in rabbit and rat models. However, the outcome is suboptimal and the technology needs to provide a more reliable and uniform outcome. To this end, we investigated whether the timing of Ad.BMP-2 administration influenced the formation of mineralized tissue within the defect. Critical-sized defects were created in the femora of 28 Sprague–Dawley rats. Animals were injected intralesionally with a single, percutaneous injection of Ad.BMP-2 (4 × 10
8
plaque-forming units) either intraoperatively (day 0) or 24 h (day 1), 5 days or 10 days after surgery. The femora were evaluated 8 weeks after surgery by X-ray, microcomputed tomography, dual-energy X-ray absorptiometry and biomechanical testing. The incidence of radiological union was markedly increased when administration of Ad.BMP-2 was delayed until days 5 and 10, at which point 86% of the defects healed. These time points also provided greater bone mineral content within the defect site and improved the average mechanical strength of the healed bone. Thus, delaying the injection of Ad.BMP-2 until 5 or 10 days after surgery enables a greater percentage of critical-sized, segmental defects to achieve radiological union, producing a repair tissue with enhanced mineralization and greater mechanical strength.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animal models</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Bone and Bones - metabolism</subject><subject>Bone and Bones - pathology</subject><subject>Bone diseases</subject><subject>Bone growth</subject><subject>Bone mineral content</subject><subject>Bone Morphogenetic Protein 2</subject><subject>Bone morphogenetic proteins</subject><subject>Bone Morphogenetic Proteins - genetics</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Bone Regeneration</subject><subject>Bone surgery</subject><subject>Bones</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Computed tomography</subject><subject>Dual energy X-ray absorptiometry</subject><subject>Fracture Fixation - methods</subject><subject>Fracture Healing</subject><subject>Fractures, Bone - metabolism</subject><subject>Fractures, Bone - pathology</subject><subject>Fractures, Bone - therapy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Genetic vectors</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injection</subject><subject>Male</subject><subject>Mechanical properties</subject><subject>Medical sciences</subject><subject>Mineralization</subject><subject>Models, Animal</subject><subject>Nanotechnology</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Surgery</subject><subject>Transduction, Genetic - methods</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Transfusions. Complications. Transfusion reactions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animal models</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Bone and Bones - metabolism</topic><topic>Bone and Bones - pathology</topic><topic>Bone diseases</topic><topic>Bone growth</topic><topic>Bone mineral content</topic><topic>Bone Morphogenetic Protein 2</topic><topic>Bone morphogenetic proteins</topic><topic>Bone Morphogenetic Proteins - genetics</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>Bone Regeneration</topic><topic>Bone surgery</topic><topic>Bones</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Computed tomography</topic><topic>Dual energy X-ray absorptiometry</topic><topic>Fracture Fixation - methods</topic><topic>Fracture Healing</topic><topic>Fractures, Bone - metabolism</topic><topic>Fractures, Bone - pathology</topic><topic>Fractures, Bone - therapy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Genetic vectors</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Injection</topic><topic>Male</topic><topic>Mechanical properties</topic><topic>Medical sciences</topic><topic>Mineralization</topic><topic>Models, Animal</topic><topic>Nanotechnology</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Surgery</topic><topic>Transduction, Genetic - methods</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Betz, O B</creatorcontrib><creatorcontrib>Betz, V M</creatorcontrib><creatorcontrib>Nazarian, A</creatorcontrib><creatorcontrib>Egermann, M</creatorcontrib><creatorcontrib>Gerstenfeld, L C</creatorcontrib><creatorcontrib>Einhorn, T A</creatorcontrib><creatorcontrib>Vrahas, M S</creatorcontrib><creatorcontrib>Bouxsein, M L</creatorcontrib><creatorcontrib>Evans, C H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Betz, O B</au><au>Betz, V M</au><au>Nazarian, A</au><au>Egermann, M</au><au>Gerstenfeld, L C</au><au>Einhorn, T A</au><au>Vrahas, M S</au><au>Bouxsein, M L</au><au>Evans, C H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>14</volume><issue>13</issue><spage>1039</spage><epage>1044</epage><pages>1039-1044</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>The direct, local, administration of adenovirus carrying human BMP-2 cDNA (Ad.BMP-2) heals critical-sized femoral bone defects in rabbit and rat models. However, the outcome is suboptimal and the technology needs to provide a more reliable and uniform outcome. To this end, we investigated whether the timing of Ad.BMP-2 administration influenced the formation of mineralized tissue within the defect. Critical-sized defects were created in the femora of 28 Sprague–Dawley rats. Animals were injected intralesionally with a single, percutaneous injection of Ad.BMP-2 (4 × 10
8
plaque-forming units) either intraoperatively (day 0) or 24 h (day 1), 5 days or 10 days after surgery. The femora were evaluated 8 weeks after surgery by X-ray, microcomputed tomography, dual-energy X-ray absorptiometry and biomechanical testing. The incidence of radiological union was markedly increased when administration of Ad.BMP-2 was delayed until days 5 and 10, at which point 86% of the defects healed. These time points also provided greater bone mineral content within the defect site and improved the average mechanical strength of the healed bone. Thus, delaying the injection of Ad.BMP-2 until 5 or 10 days after surgery enables a greater percentage of critical-sized, segmental defects to achieve radiological union, producing a repair tissue with enhanced mineralization and greater mechanical strength.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17460719</pmid><doi>10.1038/sj.gt.3302956</doi><tpages>6</tpages></addata></record> |
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| ispartof | Gene therapy, 2007-07, Vol.14 (13), p.1039-1044 |
| issn | 0969-7128 1476-5462 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | Adenoviridae - genetics Adenovirus Adenoviruses Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animal models Animals Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Bone and Bones - metabolism Bone and Bones - pathology Bone diseases Bone growth Bone mineral content Bone Morphogenetic Protein 2 Bone morphogenetic proteins Bone Morphogenetic Proteins - genetics Bone Morphogenetic Proteins - metabolism Bone Regeneration Bone surgery Bones Care and treatment Cell Biology Computed tomography Dual energy X-ray absorptiometry Fracture Fixation - methods Fracture Healing Fractures, Bone - metabolism Fractures, Bone - pathology Fractures, Bone - therapy Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Genetic aspects Genetic Therapy - methods Genetic vectors Genetic Vectors - administration & dosage Health. Pharmaceutical industry Human Genetics Industrial applications and implications. Economical aspects Injection Male Mechanical properties Medical sciences Mineralization Models, Animal Nanotechnology original-article Physiological aspects Proteins Rabbits Rats Rats, Sprague-Dawley Rodents Surgery Transduction, Genetic - methods Transforming Growth Factor beta - genetics Transforming Growth Factor beta - metabolism Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects |
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