Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage

Evans, C.H., Liu, F.-J., Glatt, V., Hoyland, J. A., Kirker-Head, C., Walsh, A., Betz, O., Wells, J. W., Betz, V., Porter, R. M., Saad, F. A., Gerstenfeld, L. C., Einhorn, T. A., Harris, M. B. and Vrahas, M. S. (2009) Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage. European Cells and Materials, 18 96-111.

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Author Evans, C.H.
Liu, F.-J.
Glatt, V.
Hoyland, J. A.
Kirker-Head, C.
Walsh, A.
Betz, O.
Wells, J. W.
Betz, V.
Porter, R. M.
Saad, F. A.
Gerstenfeld, L. C.
Einhorn, T. A.
Harris, M. B.
Vrahas, M. S.
Title Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage
Journal name European Cells and Materials   Check publisher's open access policy
ISSN 1473-2262
Publication date 2009-12-31
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 18
Start page 96
End page 111
Total pages 16
Place of publication Clavadelstr, Davos, Switzerland
Publisher Swiss Society for Biomaterials
Language eng
Formatted abstract
We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified (“gene activated”) tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.
Keyword Adenovirus
Bone morphogenetic protein
Large segmental defects
Cartilage repair
Bone healing
Gene therapy
Animal models
Facilitated endogenous repair
Tissue engineering
Fibrodysplasia ossificans progressiva
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Publication date: July - December 2009

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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Created: Thu, 22 Sep 2011, 09:21:39 EST by Dr James Wells on behalf of UQ Diamantina Institute