Genetically modified human derived bone marrow cells for posterolateral lumbar spine fusion in athymic rats: beyond conventional autologous bone grafting.
METHODS
This experimental study consisted of four groups. In Group I, 8 animals were implanted with a collagen sponge containing 5 million human-derived bone marrow cells (HBMCs) infected with the BMP-2-containing adenovirus. In Group II, 5 animals were implanted with a collagen sponge containing 5 million HBMCs, which had been infected with an adenovirus containing the cDNA for the lacZ gene. In Group III, 5 animals were implanted with a collagen sponge containing 5 million uninfected HBMCs. In Group IV, 5 animals were implanted with a collagen sponge alone. All animals were killed at 12 weeks.


OBJECTIVE
The purpose of this study was to assess the ability of HBMCs infected with a BMP-2 adenovirus to induce a posterolateral spine in an athymic rat model.


BACKGROUND
High pseudarthrosis rates after attempted spinal arthrodesis as well as the morbidity associated with iliac crest bone graft harvest make alternative bone graft materials desirable. Alternatives include allograft bone, demineralized bone matrices, and more recently, recombinant bone morphogenetic proteins. However, high doses of the recombinant protein are required, and a single dose of recombinant protein may not induce a sufficient osteoinductive response in all patients. An alternative strategy is to genetically manipulate cells to overexpress a bone morphogenetic protein.


METHODS
HBMCs grown in culture were infected with an adenovirus containing the cDNA for BMP-2 (AdBMP-2) or the gene for beta-galactosidase (AdlacZ). Cells were implanted on the decorticated transverse processes of L4-L5 as previously described. Rats were assessed by radiographs at 4-week intervals and were killed at 12 weeks. After death, spines were explanted and assessed by manual palpation and histologic analysis.


RESULTS
Eight of eight rats implanted with AdBMP-2-infected HBMCs (Group I) were fused by radiographic evaluation and manual palpation at 12 weeks. Control groups consisted of: 5 rats implanted with the collagen sponge alone (Group II), 5 rats implanted with a collagen sponge and 5 million uninfected HBMCs (Group III), and 5 rats implanted with HBMCs infected with AdlacZ (Group IV). None of the rats in the control groups (0 of 15) developed a fusion at L4-L5.


CONCLUSIONS
This study demonstrates that human-derived bone marrow cells can be infected with a BMP-2-containing adenovirus and produce sufficient bone in vivo to fuse the lumbar spine.
Peterson
Brett
B
UCLA Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA Center for Health Sciences, Los Angeles, CA 90095, USA.
Iglesias
Roberto
R
Zhang
Jeffrey
J
Wang
Jeffrey C
JC
Lieberman
Jay R
JR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D010012:Osteogenesis / Q000235:genetics*; D011859:Radiography; D051381:Rats; D011923:Rats, Nude; D013123:Spinal Fusion / Q000379:methods*; D014161:Transduction, Genetic / Q000379:methods; 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; D016212:Transforming Growth Factor beta