骨缺损的基因治疗

Gene therapy for bone defect

目的:创伤、肿瘤及人工关节翻修手术等均可造成骨缺损。传统的治疗方法包括自体骨、异体骨和人工骨移植,但每种方法均存在一定的局限性,难以完全满足临床需要。骨缺损的基因治疗克服了传统治疗方法的局限,具有重要研究意义。资料来源:应用计算机检索Pubmed数据库1990-01/2005-04有关骨缺损的基因治疗文章,检索词“bone,gene therapy,bone morphogenetic protein”,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1994-01/2005-04期间的相关文章,检索词“骨缺损,基因治疗,骨形成蛋白,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,并开始查找全文。纳入标准:①有关骨缺损的基因治疗研究。②有关骨组织工程研究。排除标准:①重复研究;②综述文章。资料提炼:共收集到168篇有关骨缺损的基因治疗及组织工程骨方面的文章,排除重复或类似的同一研究,28篇符合研究要求。资料综合:①基因治疗骨缺损的技术选择:人骨形态发生蛋白基因是目前骨缺损基因治疗中应用最多的目的基因,已在兔、鼠、羊和狗模型中证实其对骨缺损的修复作用。各种研究中,靶细胞多采用骨髓基质细胞,载体多选用腺病毒。②基因治疗骨缺损研究进展:基因治疗与组织工程相结合以及多基因联合治疗骨缺损是该领域研究的方向。③问题与展望:目前的研究大多处于实验阶段,要应用于临床还有很多工作需要改进。结论:多种细胞生长因子具有促进骨愈合的作用,通过骨缺损的基因治疗方法可保证细胞生长因子局部的靶向释放,最大限度地增加局部治疗效果,减少全身副作用,被认为是维持骨缺损局部生长因子有效治疗浓度最有希望的一种方法。

OBJECTIVE： Trauma, tumor and prosthesis of artificial joints, etc. can cause bone defect. Traditional therapies include autogenous bone, allograft bone and artificial bone grafting, but every method has some existed restriction, which is difficult to accord with the clinical requirement. The gene therapy for bone defect, which overcomes the restriction of traditional therapies, has fatal research significance. DATA SOURCES： A search of Pubmed database was performed using the key terms ＂bone , gene therapy,bone morphogenetic protein＂ from January 1990 to April 2005, which included the articles on gene therapy for bone defect in English. Meanwhile, we also searched the China Journal Full-text Database （CJFD） and Wanfang database for the related articles published between January 1994 and April 2005 with the key words ＂bone defect, gene therapy, bone morphogenetic protein, histological engineering＂ in Chinese. STUDY SELECTION： Data were selected primarily, and related articles accorded with the criteria were collected, and the full-texts were searched. Inclusion criteria were ①researches on gene therapy for bone defect and ②researches on histological engineering of bone. Exclusion criteria were ①repetitive researches and ②reviews. DATA EXTRACTION： 168 articles about gene therapy for bone defect and histological engineering of bone were collected. Those repetitive or similar researches were excluded, and 28 articles were accorded with the research criteria. DATA SYNTHESIS： ①Technical choice of gene therapy for bone defect： Human bone morphogenetic protein was the most often used objective gene in the gene therapy for bone defect at present, which had been identified in the models of rabbit, murine, caprine and dog in the application of plerosis of bone defect. In various researches, target cells often used marrow stromal cells （MSCs）; carriers often used adenoviruses.②Research progress of gene therapy for bone defect： The gene therapy with histological engineering as well as therapeutic alliance of multiple genes for bone defect was the research direction in that field. ③Problems and outlook： Most of the researches were in experimental phase at present, and many aspects needed to be improved if it is used in clinic. CONCLUSION： Many cellular growth factors have the effect of accelerating bone healing. The gene therapy for bone defect can protect target release at local growth factor, increase effectively the local curative effect and decrease the side effect of body, which is regarded as the most hopeful method for maintaining validly therapeutic concentration of local growth factor of bone defect.