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

Chisa Hidaka, Kohei Goshi, Bernard Rawlins, Obeneba Boachie-Adjei, Ronald Crystal

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 Adßgal (encoding the marker gene β-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.

Original languageEnglish
Pages (from-to)2049-2057
Number of pages9
JournalSpine
Volume28
Issue number18
DOIs
Publication statusPublished - 15 Sep 2003
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 7
Tissue Engineering
Bone Marrow Cells
Genetic Therapy
Allografts
Spine
Bone and Bones
Adenoviridae
Osteogenesis
Genes
Galactosidases
Gene Expression
Bone Regeneration
Articular Range of Motion
Transgenes
Fluorescent Dyes
Anatomy
Bone Marrow
Prospective Studies
Control Groups

Keywords

  • Adenovirus
  • Allograft
  • Bone morphogenetic protein-7
  • Gene therapy
  • Spine fusion

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Orthopedics and Sports Medicine

Cite this

Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone. / Hidaka, Chisa; Goshi, Kohei; Rawlins, Bernard; Boachie-Adjei, Obeneba; Crystal, Ronald.

In: Spine, Vol. 28, No. 18, 15.09.2003, p. 2049-2057.

Research output: Contribution to journalArticle

Hidaka, Chisa ; Goshi, Kohei ; Rawlins, Bernard ; Boachie-Adjei, Obeneba ; Crystal, Ronald. / Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone. In: Spine. 2003 ; Vol. 28, No. 18. pp. 2049-2057.
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