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

Overview

MeSH

  • Adenoviridae
  • Animals
  • Bone Marrow Cells
  • Bone Morphogenetic Protein 7
  • Bone Transplantation
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Genes, Reporter
  • Genetic Vectors
  • Lac Operon
  • Lumbar Vertebrae
  • Osseointegration
  • Prospective Studies
  • Rats
  • Rats, Inbred Lew
  • Recombinant Fusion Proteins
  • Transplantation, Homologous
  • Wound Healing

MeSH Major

  • Bone Marrow Transplantation
  • Bone Morphogenetic Proteins
  • Genetic Therapy
  • Spinal Fusion
  • Tissue Engineering
  • Transforming Growth Factor beta

abstract

  • 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. 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. 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. 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. 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. Addition of AdBMP-7-modified marrow cells can enhance allograft spine fusion.

publication date

  • September 15, 2003

has subject area

  • Adenoviridae
  • Animals
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Bone Transplantation
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Genes, Reporter
  • Genetic Therapy
  • Genetic Vectors
  • Lac Operon
  • Lumbar Vertebrae
  • Osseointegration
  • Prospective Studies
  • Rats
  • Rats, Inbred Lew
  • Recombinant Fusion Proteins
  • Spinal Fusion
  • Tissue Engineering
  • Transforming Growth Factor beta
  • Transplantation, Homologous
  • Wound Healing

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1097/01.BRS.0000091661.11228.C3

PubMed ID

  • 14501913

Additional Document Info

start page

  • 2049

end page

  • 2057

volume

  • 28

number

  • 18