骨组织工程中的间质干细胞：成骨活性、免疫特性、促血管化及成骨效应

摘要

背景：临床治疗由创伤、感染、肿瘤以及先天性疾病导致的骨缺损仍然是一个挑战。骨组织工程的研究，为骨缺损的治疗提供了一种新的解决办法，对治疗骨缺损具有重要的指导意义。目的：回顾近年来间质干细胞在骨组织工程中的增殖和成骨活性、免疫特性、促血管化以及在体实验的成骨效果的研究进展。方法：检索万方数据库和PubMed数据库2008年至2016年文献，检索词分别为“间质干细胞、组织工程、成骨、免疫、血管化”和“mesencgymal stem cel ，tissueengineering，osteogenesis，immuneproperty， angiogenesis”。纳入与间质干细胞、组织工程、成骨、免疫及血管化相关的研究，排除重复及陈旧文献。共检索到1772篇文章，按纳入和排除标准文献进行筛选，共纳入41篇文章进行综述分析。结果与结论：在骨组织工程中，骨髓间质干细胞与脂肪间质干细胞应用较为广泛。研究认为骨髓间质干细胞成骨活性高于脂肪间质干细胞。间质干细胞具有明显的免疫调节和组织修复能力，可减少损伤部位炎症反应，加快组织修复。间质干细胞免疫调节作用不只有免疫抑制作用，也有免疫促进作用，脂肪间质干细胞比骨髓间质干细胞具有较强的免疫调节性。低氧培养下的脂肪间质干细胞能够分泌更高的促血管生成因子，生成更多的血管结构。实验研究证实聚乳酸多孔纳米材料结合纳米碳生物材料可以明显促进骨髓间质干细胞的增殖和成骨。由于间质干细胞具有生物向性，可能成瘤分化，故间质干细胞的临床应用一直持谨慎态度。%BACKGROUND:It is stil a chal enge to repair bone defects caused by trauma, infection, tumor and congenital diseases. Bone tissue engineering is a promising method for bone defect repair showing important guiding significance in the clinic. OBJECTIVE:To review the progress of proliferation, osteogenic activity, immunogenicity, proangiogensis and in vivo osteogenic effect of mesenchymal stem cel s in bone tissue engineering. METHODS:The first author retrieved Wanfang and PubMed datebase for literatures published from 2008 to 2016, using the keywords of“mesenchymal stem cel , tissue engineering, osteogenesis, immune property, angiogenesis”in Chinese and English, respectively. Articles regarding mesenchymal stem cel s, tissue engineering, osteogenesis, immune property and angiogenesis were included, and repetitive and dated studies were excluded. Total y 1 772 articles were retrieved initial y, and in accordance with inclusion and exclusion criteria, 41 eligible articles were included for review analysis. RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cel s and adipose-derived mesenchymal stem cel s are extensively applied in bone tissue engineering. Studies have shown that the osteogenic activity of bone marrow mesenchymal stem cel s is higher than that of adipose-derived mesenchymal stem cel s, but its immune regulation effect is weaker than that of adipose-derived mesenchymal stem cel s. Mesenchymal stem cel s hold remarkable immune regulation (immunosuppression and immune enhancement) and tissue repair capacity, which can eliminate inflammatory reactions at injured sites, promoting tissue repair. Adipose-derived mesenchymal stem cel s cultured under hypoxia environment can secret more angiogenic cytokines generating more vascular structures. Furthermore, increasing proof have confirmed that porous nano-polylactic acid combined with nano-carbon biological material can significantly promote the proliferation and osteogenesis of bone marrow mesenchymal stem cel s. Taking its tumorigenesis into consideration, mesenchymal stem cel s should be prudently used in the clinic.