Bone morphogenetic protein gene therapy for the induction of spinal arthrodesis

1998 ◽  
Vol 4 (2) ◽  
pp. E14 ◽  
Author(s):  
Tord D. Alden ◽  
Gerald R. Hankins ◽  
Elisa J. Beres ◽  
David F. Kallmes ◽  
Gregory A. Helm

Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion. Twelve athymic nude rats were used in this study. Recombinant, replication-defective type-5 adenovirus with a universal promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with a universal promoter and ß-galactosidase (ß-gal) gene (Ad-ß-gal) was used as a control. Seven and one-half microliters of virus was injected percutaneously and paraspinally at the lumbosacral junction in three groups (four animals each): 1) Ad-BMP-2 bilaterally, 2) Ad-BMP-2 on the right, Ad-ß-gal on the left, and 3) Ad-ß-gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spine were obtained at 3, 5, and 12 weeks. At 12 weeks, the animals were killed for histological inspection. Ectopic bone formation was seen both on three-dimensional CT reconstruction and histologically in all rats at sites treated with Ad-BMP-2. Histological analysis revealed bone at different stages of maturity adjacent to the spinous processes, laminae, and transverse processes. This study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that gene therapy may be useful for spinal fusion in the future.

1999 ◽  
Vol 90 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Tord D. Alden ◽  
Debra D. Pittman ◽  
Elisa J. Beres ◽  
Gerald R. Hankins ◽  
David F. Kallmes ◽  
...  

Object. Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion. Methods. Twelve athymic nude rats were used in this study. Recombinant, replication-defective type 5 adenovirus with the cytomegalovirus (CMV) promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with the CMV promoter and β-galactosidase (β-gal) gene (Ad-β-gal) was used as a control. In three groups (four rats each) 7.5 µl of virus (5 × 108 particles/µl) was injected percutaneously and paraspinally at the lumbosacral junction: Group 1 received Ad-BMP-2 bilaterally; Group 2 received Ad-BMP-2 on the right, Ad-β-gal on the left; and Group 3 received Ad-β-gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spine were obtained at 3, 5, 8, and 12 weeks. At 12 weeks, the animals were killed and underwent histological inspection. Ectopic bone formation was observed both on three-dimensionally reconstructed CT scans and histological examination in all rats at sites treated with Ad-BMP-2. Histological analysis demonstrated bone at different stages of maturity adjacent to the spinous processes, laminae, and transverse processes. Conclusions. Results of this study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that gene therapy may be useful for spinal fusion in the future.


2005 ◽  
Vol 11 (3-4) ◽  
pp. 645-658 ◽  
Author(s):  
Catherine M. Cowan ◽  
Oliver O. Aalami ◽  
Yun-Ying Shi ◽  
Yu-Fen Chou ◽  
Carina Mari ◽  
...  

2015 ◽  
Vol 21 (9-10) ◽  
pp. 1672-1679 ◽  
Author(s):  
Loek D. Loozen ◽  
Yvonne J.M. van der Helm ◽  
F. Cumhur Öner ◽  
Wouter J.A. Dhert ◽  
Moyo C. Kruyt ◽  
...  

2007 ◽  
Vol 42 (3) ◽  
pp. 267-273 ◽  
Author(s):  
J. D. Bradley ◽  
D. G. Cleverly ◽  
A. M. Burns ◽  
N. B. Helm ◽  
M. J. Schmid ◽  
...  

Gene Therapy ◽  
2003 ◽  
Vol 10 (16) ◽  
pp. 1345-1353 ◽  
Author(s):  
Y Chen ◽  
K D K Luk ◽  
K M C Cheung ◽  
R Xu ◽  
M C Lin ◽  
...  

2020 ◽  
Vol 21 (17) ◽  
pp. 6425
Author(s):  
Songhyun Lim ◽  
Hao-Zhen Lyu ◽  
Ju-Ro Lee ◽  
Shi Huan Han ◽  
Jae Hyup Lee ◽  
...  

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.


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