Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone.

Publication Type	Academic Article
Authors	Hidaka C, Goshi K, Rawlins B, Boachie-Adjei O, Crystal R
Journal	Spine (Phila Pa 1976)
Volume	28
Issue	18
Pagination	2049-57
Date Published	09/15/2003
ISSN	1528-1159
Keywords	Bone Marrow Transplantation, Bone Morphogenetic Proteins, Genetic Therapy, Spinal Fusion, Tissue Engineering, Transforming Growth Factor beta
Abstract	STUDY DESIGN: 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. OBJECTIVES: 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. SUMMARY OF BACKGROUND DATA: 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. MATERIALS AND 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.
DOI	10.1097/01.BRS.0000091661.11228.C3
PubMed ID	14501913