TY - JOUR
T1 - pCMV-BMP-2-Transfected Cell-Mediated Gene Therapy in Anterior Cruciate Ligament Reconstruction in Rabbits
AU - Wang, Ching Jen
AU - Weng, Lin Hsiu
AU - Hsu, Shan Ling
AU - Sun, Yi Chih
AU - Yang, Ya Ju
AU - Chan, Yi Sheng
AU - Yang, Yu Lin
PY - 2010/7
Y1 - 2010/7
N2 - Purpose: This study investigated the effect of plasmid cytomegalovirus (pCMV)-bone morphogenetic protein 2 (BMP-2) gene therapy on the healing of the tendon-bone interface after anterior cruciate ligament (ACL) reconstruction in rabbits. Methods: The pCMV-BMP-2 was synthesized from full-length human BMP-2 complementary deoxyribonucleic acid, followed by cloning into pCMV Script vector (Clontech Laboratories, Inc., San Jose, CA), and was delivered by a xenogeneic (rat kidney) cell line. The ACL was reconstructed by the transfer of extensor digital tendon in the proximal tibia. In the study group the pCMV-BMP-2 gene-transfected normal rat kidney cells mixed with calcium alginate gel were placed at the tendon-bone interface, whereas no pCMV-BMP-2 was used in the control group. The evaluations included radiography, bone mineral density, magnetic resonance imaging, biomechanical study, histologic examination, and immunohistochemical analysis. Results: Bone mineral density showed no significant difference between the groups (P > .05). Magnetic resonance imaging showed significantly better contact between tendon and bone in the study group compared with the control group (P < .0001). In the biomechanical study, significantly higher failure load and maximal graft tension were noted in the study group compared with the control group (P = .034). The modes of graft failure were rupture of the tendon proper in 78% and graft pullout from the bone tunnel in 22% of specimens in the study group versus graft rupture in 22% and graft pullout in 78% in the control group (P = .018). On histologic examination, the study group showed significantly better integration between tendon and bone, as well as more bone tissue around the tendon graft, than the control group (P = .0004). On immunohistochemical analysis, the study group showed significantly higher expressions of von Willebrand factor, vascular endothelial growth factor, proliferation cell nuclear antigen, and BMP-2 than the control group (P < .05). Conclusions: The pCMV-BMP-2 gene therapy significantly improved the healing of tendon to bone and promoted angiogenesis and osteogenesis at the tendon-bone interface after ACL reconstruction in the rabbit model. Clinical Relevance: Application of pCMV-BMP-2 gene therapy may be an effective adjunct therapy in ACL reconstruction.
AB - Purpose: This study investigated the effect of plasmid cytomegalovirus (pCMV)-bone morphogenetic protein 2 (BMP-2) gene therapy on the healing of the tendon-bone interface after anterior cruciate ligament (ACL) reconstruction in rabbits. Methods: The pCMV-BMP-2 was synthesized from full-length human BMP-2 complementary deoxyribonucleic acid, followed by cloning into pCMV Script vector (Clontech Laboratories, Inc., San Jose, CA), and was delivered by a xenogeneic (rat kidney) cell line. The ACL was reconstructed by the transfer of extensor digital tendon in the proximal tibia. In the study group the pCMV-BMP-2 gene-transfected normal rat kidney cells mixed with calcium alginate gel were placed at the tendon-bone interface, whereas no pCMV-BMP-2 was used in the control group. The evaluations included radiography, bone mineral density, magnetic resonance imaging, biomechanical study, histologic examination, and immunohistochemical analysis. Results: Bone mineral density showed no significant difference between the groups (P > .05). Magnetic resonance imaging showed significantly better contact between tendon and bone in the study group compared with the control group (P < .0001). In the biomechanical study, significantly higher failure load and maximal graft tension were noted in the study group compared with the control group (P = .034). The modes of graft failure were rupture of the tendon proper in 78% and graft pullout from the bone tunnel in 22% of specimens in the study group versus graft rupture in 22% and graft pullout in 78% in the control group (P = .018). On histologic examination, the study group showed significantly better integration between tendon and bone, as well as more bone tissue around the tendon graft, than the control group (P = .0004). On immunohistochemical analysis, the study group showed significantly higher expressions of von Willebrand factor, vascular endothelial growth factor, proliferation cell nuclear antigen, and BMP-2 than the control group (P < .05). Conclusions: The pCMV-BMP-2 gene therapy significantly improved the healing of tendon to bone and promoted angiogenesis and osteogenesis at the tendon-bone interface after ACL reconstruction in the rabbit model. Clinical Relevance: Application of pCMV-BMP-2 gene therapy may be an effective adjunct therapy in ACL reconstruction.
UR - http://www.scopus.com/inward/record.url?scp=77953945232&partnerID=8YFLogxK
U2 - 10.1016/j.arthro.2009.11.014
DO - 10.1016/j.arthro.2009.11.014
M3 - 文章
C2 - 20620796
AN - SCOPUS:77953945232
SN - 0749-8063
VL - 26
SP - 968
EP - 976
JO - Arthroscopy - Journal of Arthroscopic and Related Surgery
JF - Arthroscopy - Journal of Arthroscopic and Related Surgery
IS - 7
ER -