Adenoviral BMP-2 Gene Transfer in Mesenchymal Stem Cells: In Vitro and in Vivo Bone Formation on Biodegradable Polymer Scaffolds

Partridge, Kris; Yang, Xuebin; Clarke, Nicholas; Okubo, Yasunori; Bessho, Kazuhisa; Sebald, Walter; Howdle, Steven M.; Shakesheff, Kevin M.; Oreffo, Richard O.C.

doi:10.1006/bbrc.2002.6623

Cited by 162 publications

(105 citation statements)

References 40 publications

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“…MSCs appear reasonably receptive to transduction with recombinant adenoviral vectors, [90][91][92] retrovirus, 33,93 lentivirus and AAV (unpublished observation). Currently, several laboratories are studying means to apply this technology to MSCs in vivo.…”

Section: Gene Transfer To Chondroprogenitor Cellsmentioning

confidence: 85%

Gene-based approaches for the repair of articular cartilage

2004

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Section: Gene Transfer To Chondroprogenitor Cellsmentioning

confidence: 85%

Gene-based approaches for the repair of articular cartilage

2004

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“…The identification of BMPs has generated great interest due to their potential use in bone regeneration. 3 Several recombinant forms of BMPs, mostly rhBMP-2 and rhBMP-7 (a.k.a., OP-1), have been shown to induce bone formation in vivo, [13][14][15][16][17][18][19][20][21][22][23][24] and both rhBMP-2 and rhBMP-7 have been tested in clinical trials. [25][26][27] In addition to the direct application of recombinant BMP proteins, numerous reports have confirmed the ability of adenoviral or retroviral vector-mediated gene transfer of several BMPs to induce bone formation in animal models.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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“…The BMP viral vectors include recombinant adenovirus, retrovirus and baculovirus. 13,[28][29][30][31][32][33] Gysin et al 34 demonstrated that recombinant BMP-4 retrovirus-transduced stromal cells embedded in a gelatin matrix could heal critical size defects in calvariae of syngeneic rats. Gelatin matrices without cells and with untransduced stromal cells were the two control groups.…”

Section: Introductionmentioning

confidence: 99%

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

et al. 2003

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one morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 Â 10 5 PFU/well of BMP viral vector was 4890 Â 10 À12 U/well for ADCMVBMP-9, 302 Â 10 À12 U/well for ADCMVBMP-4, 220 Â 10 À12 U/well for ADCMVBMP-6, 45 Â 10 À12 U/well for ADCMVBMP-2, and 0.43 Â 10 À12 U/ well for ADCMVBMP-7. The average volume of new bone induced by 10 7 PFU of BMP vector in athymic nude rats was 0.3770.03 cm 3 for ADCMVBMP-2, 0.8970.07 cm 3 for ADCMVBMP-4, 1.0270.07 cm 3 for ADCMVBMP-6, 0.2470.05 cm 3 for ADCMVBMP-7, and 0.6370.07 cm 3 for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10 8 PFU induced 0.1070.03 cm 3 of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10 7 PFU induced more bone, with an average volume of 0.2970.01 cm 3 .

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Adenoviral BMP-2 Gene Transfer in Mesenchymal Stem Cells: In Vitro and in Vivo Bone Formation on Biodegradable Polymer Scaffolds

Cited by 162 publications

References 40 publications

Gene-based approaches for the repair of articular cartilage

Gene-based approaches for the repair of articular cartilage

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

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