Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone.
METHODS
Prospective study to assess the enhancement of spine fusion using a tissue engineering construct consisting of bone marrow cells genetically modified by adenovirus (Ad) vector-encoding bone morphogenetic protein-7 (BMP-7) seeded onto an allograft scaffold in a rat model.


OBJECTIVE
To evaluate Ad transgene expression at the fusion site and the effect of AdBMP-7-treatment on fusion rates, mechanical stability, microscopic anatomy, and bone formation rates.


BACKGROUND
Nonunion is a major complication of spine fusion. Gene transfer may be an effective method for locally overexpressing BMP-7, a gene important for bone formation and regeneration to enhance allograft spine fusion.


METHODS
Bone marrow cells were treated with AdBMP-7 or Adbetagal (encoding the marker gene beta-galactosidase), AdNull (with no gene), or no vector and implanted with allograft in a site of posterior spine fusion. Marker gene expression was assessed up to 14 days after administration. Fusions were evaluated at 8 weeks.


RESULTS
Ad gene expression was maximal on day 3, waning to background levels by 14 days. With AdBMP-7 treatment, radiographic fusion rate was 70% and mechanical fusion rate was 80% versus 0% by either parameter in control groups. Fused AdBMP-7-treated spines had a 2.5-fold to 3.0-fold lower range of motion and 1.7-fold to 1.9-fold lower hysteresis than controls. Fusion masses of AdBMP-7-treated spines had the microscopic appearance of normal trabecular bone and showed a 23-fold higher uptake of fluorochrome indicating increased bone formation.


CONCLUSIONS
Addition of AdBMP-7-modified marrow cells can enhance allograft spine fusion.
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D016025:Bone Transplantation; D002478:Cells, Cultured / Q000378:metabolism / Q000637:transplantation; D004353:Drug Evaluation, Preclinical; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D007763:Lac Operon; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery / Q000648:ultrastructure; D016348:Osseointegration; D011446:Prospective Studies; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013123:Spinal Fusion / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014184:Transplantation, Homologous; D014945:Wound Healing
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta