A gene therapy approach to accelerating bone healing. Evaluation of gene expression in a New Zealand white rabbit model.

A. W. Baltzer, C. Lattermann, J. D. Whalen, S. Braunstein, P. D. Robbins, C. H. Evans

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

It has been demonstrated that BMPs, IGFs, and TGFbetas improve the process of bone healing in vivo. We have suggested the use of gene therapy as a possible way to deliver growth factors to fracture sites in order to improve repair. The aim of this study was to develop a minimally invasive gene therapy approach to treat bone injuries locally without damaging the local blood circulation. A segmental defect of 1.3 cm was created in the diaphysis of the femur in mature NZW rabbits. Internal fixation with 7-hole DCP plates and 2.7 mm screws was used to stabilize the bone. After building a chamber by tightly closing the muscles around the segmental defect, 0.5 ml of either saline solution or a collagen gel containing 1 x 10(10) particles of adenovirus carrying cDNA encoding either the bacterial beta-galactosidase gene (LacZ), or the firefly luciferase gene were injected into the gap. The control side received 0.5 ml of saline solution without virus particles. Bone marrow, cortical and trabecular bone and surrounding muscle were harvested from the injected femur and were analyzed for local gene expression through X-gal staining or measurement of local luciferase activity. To determine whether distant sites were transduced, tissue from the spleen, liver, and lung were harvested as well as bone, bone marrow and muscle from the contralateral diaphysis of the femur. The delivery of the adenoviral vector suspended in saline solution led to local transduction of the bone, bone marrow and the muscle surrounding the gap. No luciferase activity was found in the contralateral femur, lung, or spleen, and only transient luciferase activity was seen in the liver. While marker gene expression persisted within the surrounding soft tissues for at least 2 weeks, the expression in bone lasted up to 6 weeks. This study has shown that it is possible to use adenoviral vectors to transfer and express genes locally within a segmental defect. Gene expression persisted for several weeks, which may be already sufficient to accelerate repair.

Original languageEnglish (US)
Pages (from-to)197-202
Number of pages6
JournalKnee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
Volume7
Issue number3
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'A gene therapy approach to accelerating bone healing. Evaluation of gene expression in a New Zealand white rabbit model.'. Together they form a unique fingerprint.

Cite this