Regional gene therapy of bone defects
Xu Wei-dong, Zhao Jian-guo Department of Orthopaedics, Changhai Hospital, Second Military Medical University of Chinese PLA, Shanghai 200433, China
BACKGROUND: The regional gene therapy of bone defect is to transfer genes capable of accelerating bone healing into target cells, which will transcript the genes into mRNA and translate them into proteins, then the target cells will be stimulated to differentiate under the role of protein, and finally reach the purpose of accelerating bone healing by means of autocrine or paracrine. With the development of cell recombination technique, more and more genes of growth factors involved in the bone repairing have been successfully cloned, which make it possible to treat bone defect with gene therapy. The present status for the regional gene therapy of bone defect is summarized. DATA SOURCES: An online search in Pubmed database was undertaken to identify articles about the regional gene therapy of bone defect published in English from January 1965 to January 2006 by using keywords of "gene therapy, bone defect". Meanwhile, Chinese relevant articles published from January 2000 to January 2006 were searched in Wanfang database by using the same keywords in Chinese. STUDY SELECTION: The data were primarily checked, and the references of each article were looked up. Inclusive criteria: related to the regional gene therapy of bone defect. Exclusive criteria: repetitive study or Meta analysis. DATA EXTRACTION: Totally 237 articles were collected, 32 of them were in accordance with the inclusive criteria, and the other 205 were old or repetitive ones. Of the 32 articles, 4 were about the selection of destination genes, 3 about the selection of target cells, 7 about the selection of gene expression vector, 3 about the methods of gene transfer, 4 about gene therapy combined with tissue engineering in treating bone defect, 5 about polygenes in treating bone defects, and 2 about the problems and prospects in the gene therapy of bone defect. DATA SYNTHESIS: The regional gene therapy of bone defect is a new technique developed base on the basic theoretical cognition of bone regeneration and gene recombination technique, and provides ideal solving program for the treatment of bone defect caused by various reasons. The basic problems mainly include the selection of destination genes, selection of target cells, selection of gene expression vectors and the selection of the methods of gene transfer. The studies about the selection of target cells and methods of gene transfer become mature day by day, bone marrow stromal cells have become the target cells should be selected firstly, and it has been generally acknowledged that ex vivo gene transfer has more obvious advantages than in vivo one. The key problem at present is how to further explain the natural process of the repair of bone defect, and select the most effective component from the signal molecules involved in the process to apply in the gene therapy of bone defect, and further improve the gene expression vector, so as to ensure the safety of gene therapy. It is believed that with the continuously deepened theoretical cognition of bone regeneration and the continuous perfection of gene recombinant technique, the gene therapy of bone defect will finally go out of laboratory, and really serve the patients with bone defect. CONCLUSION: The regional gene therapy of bone defect can effectively activate the activity of bone regeneration at the site of bone defect, also can avoid the problems of immunologic rejection and systematic toxicity caused by the direct application of cytokines, and has good prospects of clinical application. At present, this technique is not completely perfect, and there are many problems to be deeply investigated in destination genes, gene vectors and transfection technique, etc.
【CateGory Index】： R68