Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats

W. K. Hsu, O. Sugiyama, S. H. Park, A. Conduah, B. T. Feeley, N. Q. Liu, L. Krenek, M. S. Virk, D. S. An, I. S. Chen, J. R. Lieberman*

*Corresponding author for this work

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5 × 106 rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1 × 106 RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p < 0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p < 0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo.

Original languageEnglish (US)
Pages (from-to)931-938
Number of pages8
JournalBone
Volume40
Issue number4
DOIs
StatePublished - Apr 1 2007

Keywords

  • BMP-2
  • Bone
  • Bone morphogenetic protein
  • Femoral defect
  • Gene therapy
  • Lentivirus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Hsu, W. K., Sugiyama, O., Park, S. H., Conduah, A., Feeley, B. T., Liu, N. Q., Krenek, L., Virk, M. S., An, D. S., Chen, I. S., & Lieberman, J. R. (2007). Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats. Bone, 40(4), 931-938. https://doi.org/10.1016/j.bone.2006.10.030