Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy (Nature Medicine, 11(3):291-297, Mar.2005)

報告日期: 2005/11/04
報告時間: 15:10/16:00
報告學生: 陳世堯
講評老師: 呂增宏
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Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

 

Nature Medicine 11:291-297(2005)

 

Speaker: 陳世堯                                         Date: 2005/11/04

Commentator: 呂增宏 老師                               Place: Room 602

 

Abstract:

Structure bone grafting is commonly used in orthopedic reconstruction surgeries such as spinal fusion, repair of skeletal defects following removal of tumor. Both experimental and clinical studies have shown that fresh autografts are superior to allografts in graft repair and remodeling because the former contain living cells. However, structural allografts are readily available due to those derived from cadavers. In order to investigate the signals deficient in allograft healing and make them more clinical useful, the authors firstly developed a murine segmental femoral graft model. According to the previous microarray gene expression profiling studies on fracture callus tissue, they performed a screen by RT-PCR to identify that two factors, RANKL and VEGF, showed most substantial differential gene expression between autografts and allografts. Micorarray studies using RNA isolated from autografts and allografts confirmed the result that these transcripts were presented in the autografts and absent in allografts. Loss of function studies showed that both factors are required for autograft healing and play important roles in graft vascularization and remodeling. To determine if the introduction of these two genes into allograft could stimulate these two phenomenon for graft healing, the authors developed a new gene-delivery system in which  rAAV could be freeze-dried onto the graft surface without lose of infectivity. The results indicate that combinational rAAV-RANKL and rAAV-VEGF-coated allografts show obvious vascularization and remodeling, which eventually lead to new cortical bone formation around the implanted grafts.     

 

Reference:

1.        Tiyapatanaputi, P. et al. A novel murine segmental femoral graft model. J orthop Res          

22, 1254-1260 (2004).

2.  Hadjiargyrou, M. et al. Transcriptional profiling of bone regeneration. Insight into molecular complexity of wound repair. J. Biol Chem. 277, 30177-30182 (2002).