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骨髓间充质干细胞的生物学特性及其临床治疗应用

Biological characteristics and clinical application of bone marrow mesenchymal stem cells

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【作者】 邱林金先庆

【Author】 Qiu Lin, Jin Xian-qingDepartment of Ortho- paedic Surgery, Chil- dren’s Hospital, Chongqing Medical University, Chongqing 400014, China

【机构】 重庆医科大学儿童医院整形外科重庆医科大学儿童医院整形外科 重庆市400014重庆市400014

【摘要】 学术背景:骨髓间充质干细胞是来源于骨髓基质的一类具有自我更新能力、可分化为中胚层细胞系的干细胞。可分化为组成组织功能细胞的内在能力,使它们成为细胞和基因治疗的潜在来源。目的:综述骨髓间充质干细胞的生物学特性和治疗应用的研究进展。检索策略:应用计算机检索Pubmed1999-01/2006-12期间相关文章,检索词为"Bonemarrowmesenchymalstemcells,genetherapy,transplant",并限定文章语言种类为English。同时机检索万方数据库1999-01/2006-12期间相关文章,检索词为"骨髓间充质干细胞,基因治疗,移植"。对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与骨髓间充质干细胞生物学特性、治疗中应用相关进展研究。排除标准:重复研究或Meta分析类文章。共收集到95篇相关文献,78篇文献符合纳入标准,排除的45篇为内容陈旧或重复文献。文献评价:文献的来源主要是骨髓间充质干细胞的各种生物学特性、细胞移植、基因治疗等基础和临床相关研究。选用符合纳入标准78篇文献中的33篇,4篇关于骨髓间充质干细胞分离,3篇关于骨髓间充质干细胞的表面标志,6篇关于骨髓间充质干细胞生物学特性,3篇关于骨髓间充质干细胞移植与宿主间的免疫反应,17篇关于骨髓间充质干细胞在疾病治疗中的运用。资料综合:骨髓间充质干细胞在合适条件下可分化为骨、软骨、脂肪、肌肉、肌腱、神经样细胞、心肌细胞、支持造血干细胞的基质细胞等多种细胞。研究表明,由于骨髓间充质干细胞具有免疫抑制性和非常低的免疫原性,骨髓间充质干细胞被用于实验和临床的治疗研究中,主要包括4个方面的应用:局部移植;系统移植;结合干细胞的基因治疗;组织工程领域中的应用。尽管目前的研究大部分在动物实验中,但部分临床运用已取得了成功,这些有效的结果尚需临床足够的随机患者的研究。结论:对骨髓间充质干细胞生物学特性已有了一定的认识,这对其运用于临床治疗提供了坚实基础,随着对其特性的不断揭示,骨髓间充质干细胞在临床治疗应用中有着理想前景。

【Abstract】 BACKGROUND: Mesenchymal stem cells from bone marrow stroma are able to differentiate into multiple mesoderm-type cell lineages. Because of the ease of their isolation and their extensive differentiated potentiality, mesenchymal stem cells become potential resource of cell and gene therapy. OBJECTIVE: To summarize biological characteristics and application of bone marrow mesenchymal stem cells. RETRIEVAL STRATEGY:An online search of Pubmed was undertaken by using the keywords of "Bone marrow mesenchymal stem cells, gene therapy, transplant"to identify the relevant articles published in English from January 1999 to December 2006. At the same time,Wanfang database was undertaken to identify the relevant articles published between January 1999 and December 2006 with the key words of "Bone marrow mesenchymal stem cells, gene therapy, transplant" in Chinese.The data were selected primarily, and then quotations of each article were checked. Inclusive criterion:The articles related to the biological characteristics and application of bone marrow mesenchymal stem cells were included. Exclusive criteria:the articles with repetitive research or Meta analysis were excluded.Totally 95 relevant articles were selected and 78 of them met the inclusive criterion. The 45 excluded articles were of old or repetitive content. LITERATURE EVALUATION: Selected articles were on basic experiment or clinical study of the biological characteristics, cell transplantation and gene therapy of bone marrow mesenchymal stem cells. Totally 33 articles of the 78 articles met the inclusive criterion were included. Of them, 4 articles were on the isolation of bone marrow mesenchymal stem cells, 3 on surface marker of bone marrow mesenchymal stem cells, 6 on biological characteristics of bone marrow mesenchymal stem cells, 3 on immune response between bone marrow mesenchymal stem cell transplantation and host and 17 on the application of bone marrow mesenchymal stem cells on disease therapy. DATA SYNTHESIS: In the suitable condition, bone marrow mesenchymal stem cells can differentiate into multiple cells, such as bone, chondrocytes, fat, muscle, tendon, neuron-like cells, myocardial cells and stroma-cells that support hematopoietic stem cells. Bone marrow mesenchymal stem cells seem to be the cells of immunosuppression and low-down immunogenicity. It makes bone marrow mesenchymal stem cells used in systemic transplantation, local implantation, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues and organs in tissue engineering protocols. The results of these initial trials are very encouraging in animal test and several clinical trials are successful in some patients. But the enough clinical trails and long-term safety of therapeutics based on bone mesenchymal stem cells are needed. CONCLUSION: Biological characteristics of bone marrow mesenchymal stem cells have been gradually recognized. It is hoped that using bone marrow mesenchymal stem cells in clinic will bring major advances in the therapy of some diseases.

【关键词】 骨髓间充质干细胞; 基因治疗; 移植;

【分类号】R329.24;R97;R456.9;

【基金】 重庆市卫生局医学科技计划项目(06-165)资助~~

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