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

W. Lattanzi, C. Parrilla, A. Fetoni, G. Logroscino, G. Straface, G. Pecorini, E. Stigliano, A. Tampieri, R. Bedini, R. Pecci, F. Michetti, A. Gambotto, P. D. Robbins, E. Pola

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1330-1343
Number of pages14
JournalGene Therapy
Volume15
Issue number19
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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