Comparison of lentiviral and adenoviral gene therapy for spinal fusion in rats.
METHODS
Rat spinal fusion model.


OBJECTIVE
This study aimed to compare the efficacy of lentiviral gene therapy, and adenoviral gene therapy in inducing spinal fusion in an immune competent rat spinal fusion model.


BACKGROUND
Recombinant bone morphogenetic proteins (BMPs) have also been used for spinal fusion successfully in clinical trials. However, large doses of BMPs are required to induce adequate bone repair. Hence, regional gene therapy may be a more efficient method to deliver proteins to a specific anatomic site. Recently, lentiviral vectors based on human immunodeficiency virus have been developed for gene therapy. However, lentiviral gene therapy for spinal fusion has not been compared with adenoviral gene therapy.


METHODS
Lewis rats were divided into 7 groups. group I, II, III, and IV rats were implanted with a collagen sponge containing rat bone marrow cells (RBMCs) transfected with Lenti-BMP-2, Adeno-BMP-2, Lenti-GFP, Adeno-LacZ, respectively. Group V, VI, and VII rats were implanted with a collagen sponge containing recombinant BMP-2, a collagen sponge containing untransfected RBMCs, and a collagen sponge alone, respectively. The rats were assessed at 4, 6, and 8 weeks after implantation. After sacrificing the rats, their spines were explanted and assessed by manual palpation, high-resolution microcomputed tomography, and histologic analysis.


RESULTS
Spinal fusion was observed in all animals in group I, II, and V rats at 8 weeks. None of the rats in groups III, IV, VI, and VII showed spinal fusion. The volumes of the new bone in the area between the L4 and L5 transverse processes were greater in group I rats than in group II, and V rats with a significant difference.


CONCLUSIONS
BMP-2-producing RBMCs developed using lentiviral gene transfer induced more abundant bone within the fusion mass than the RBMCs transduced via adenoviral gene transfer and recombinant protein therapy.
Miyazaki
Masashi
M
Department of Orthopaedic Surgery, UCLA Comprehensive Spine Center, University of California at Los Angeles, CA, USA.
Sugiyama
Osamu
O
Zou
Jun
J
Yoon
Seung Hwan
SH
Wei
Feng
F
Morishita
Yuichiro
Y
Sintuu
Chananit
C
Virk
Mandeep S
MS
Lieberman
Jay R
JR
Wang
Jeffrey C
JC
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015316:Genetic Therapy; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D010012:Osteogenesis; D010173:Palpation; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000378:metabolism; D013123:Spinal Fusion / Q000379:methods*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta