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Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models

Gene Therapy volume 15, pages 1330–1343 (2008)Cite this article

Abstract

Local gene transfer of the human Lim mineralization protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. To develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP-3 and seeded on a hydroxyapatite/collagen matrix prior to autologous implantation. Here, we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing, as determined by X-rays, histology and three-dimensional microcomputed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3 in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.

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Acknowledgements

Enrico Pola was supported by a grant of the Italian Society of Orthopaedics and Traumatology. We thank Kaori Okada and Sun Huijie (Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA), and Alessandro Sbriccoli (Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Rome, Italy), for their invaluable technical assistance.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy

    W Lattanzi & F Michetti

  2. Department of Otolaryngology, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy

    C Parrilla & A Fetoni

  3. Department of Orthopaedics, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy

    G Logroscino & E Pola

  4. Department of Internal Medicine, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy

    G Straface & G Pecorini

  5. Department of Pathology, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy

    E Stigliano

  6. Department of Science and Technology for Ceramics ISTEC-CNR National Council of Research, Faenza, Italy

    A Tampieri

  7. Technology and Health Department, Istituto Superiore di Sanità, Rome, Italy

    R Bedini & R Pecci

  8. Latium Musculoskeletal Tissue Bank, Rome, Italy

    F Michetti

  9. Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    A Gambotto & P D Robbins

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  1. W Lattanzi
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Correspondence to E Pola.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Lattanzi, W., Parrilla, C., Fetoni, A. et al. Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models. Gene Ther 15, 1330–1343 (2008). https://doi.org/10.1038/gt.2008.116

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  • DOI: https://doi.org/10.1038/gt.2008.116

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