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

Wanda Lattanzi, Anna Rita Fetoni, Giovanni Pecorini, Claudio Parrilla, Giandomenico Logroscino, Giuseppe Straface, Egidio Stigliano, Fabrizio Michetti, Enrico Pola, A Tampieri, R Bedini, R Pecci, A Gambotto, Pd Robbins

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

49 Citazioni (Scopus)

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 (3DmuCT). 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.
Lingua originaleEnglish
pagine (da-a)1330-1343
Numero di pagine14
RivistaGene Therapy
Stato di pubblicazionePubblicato - 2008

Keywords

  • Lim mineralization protein-3
  • animal models

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