颅颌面部骨骼重建相关基因治疗的研究与进展

Research and progress in gene therapy for cranio-maxillofacial bone remodeling

目的:创伤、肿瘤及正颌外科手术等均可造成颅颌面的骨缺损。传统的治疗方法如自体骨移植、人工材料修复等均存在一定的局限性,难以满足临床需要。近年兴起的基因治疗克服了传统方法的局限,促进颅颌面骨骼的重建,对其研究进展进行归纳总结。资料来源:应用计算机检索Pubmed数据库1990-01/2007-04有关颅颌面骨缺损基因治疗的文章,检索词"bone,genetherapy,craniomaxillofacial,tissue engineering",限定文章语言种类为English。同时计算机检索中国期刊全文数据库、万方数据库1994-01/2007-04期间的相关文章,检索词"骨缺损、颅颌面,基因治疗,骨组织工程",限定文章语言种类为中文。资料选择:对资料进行初审,选取符合研究要求的有关文章找全文。纳入标准:①有关骨缺损基因治疗的研究。②有关组织工程骨基因治疗的研究。排除标准:重复或类似的同一研究、Meta分析、综述文献(或个案报道等)。资料提炼:共收集到235篇有关骨缺损和组织工程骨基因治疗的文章,排除重复或类似的同一研究,39篇符合研究要求。资料综合:①基因治疗促进骨骼重建的技术选择,人骨形态发生蛋白基因是目前骨骼重建相关基因治疗中应用最多的目的基因,其对骨骼重建的促进作用已在多种动物模型中得到证实。在这些研究中靶细胞多采用骨髓间充质干细胞,载体最多选用腺病毒,其次为脂质体。②基因治疗促进骨骼重建的研究进展:基因治疗与组织工程相结合以及联合基因治疗是该领域的研究方向。③问题与展望:目前研究大多是实验研究,要想用于临床还有许多问题需要解决。结论:多种细胞因子对骨骼重建有促进作用,通过基因治疗的方法可使细胞因子在局部靶向释放,最大限度地增加局部治疗效果,减少副作用。基因治疗是维持骨缺损局部生长因子有效治疗浓度的最有希望的方法。

OBJECTIVE： Trauma, tumor and orthognathic surgery can cause cranio-maxillofacial bone defect. Traditional therapies include autogenous bone grafting and artificial materials, but those methods have existed restriction, which is difficult to accord with the clinical requirement. The gene therapy for bone remodeling, which overcomes the restriction of traditional therapies, has fatal research significance, and this article was designed to summarize the study progress. DATA SOURCES：A search of Pubmed database was undertaken to identify the relevant articles on gene therapy for cranio-maxillofacial bone defect published from January 1990 to April 2007 with the keywords of ＂bone, gene therapy, cranio-maxiUofacial, tissue engineering＂ in English. Simultaneously, the China Journal Full-text Database （CJFD） and Wanfang Database were also searched for relevant articles published from January 1994 to Apnl 2007 with the keywords of ＂bone defect, cranio-maxillofacial, gene therapy, tissue engineering＂ in Chinese. STUDY SELECTION：Data were selected primarily, and related articles accorded with the criteria were collected, and the full-text were searched. Inclusive criteria were （1）researches on gene therapy for bone defect and （2）researches on bone tissue engineering by gene therapy. Exclusive criteria were repetitive or similar researches, Meta analysis and reviews （or case report）. DATA EXTRACTION：235 articles about gene therapy for bone defect and bone tissue engineering were collected. Those repetitive or similar researches were excluded, and 39 articles were accorded with the research criteria. DATA SYNTHESIS： （1）Technical choice of gene therapy for bone remodeling： Human bone morphogenetic protein was the most often used target gene in the gene therapy for bone remodeling at present. It had been identified in the many kinds of models in the application of plerosis of bone remodeling. In various researches, bone marrow mesenchymal stem cells （BMSCs） were often used as target cells, adenoviruses was often used as carriers and followed by liposomes. （2）Research progress of gene therapy for bone remodeling： The gene therapy combined with bone tissue engineering as well as multiple genes applied for bone defect was the research direction in that field. （3）Problems and outlook： Most of the researches were in experimental phase at present, and many problems needed to be improved if it was used in clinic. CONCLUSION：Many cellular growth factors have the effect of accelerating bone remodeling. The gene therapy for bone remodeling can protect target release at local growth factor, increase effectively the local curative effect and decrease the side effect of body. Gene therapy is regarded as the most helpful method for maintaining validly therapeutic concentration of local growth factor of bone remodeling.