自体软骨细胞移植技术的回顾与展望

Retrospect and prospect of autologous chondrocyte implanta-tion

目的:在过去10年中,自体软骨细胞移植技术成为治疗关节软骨缺损的最佳方案。回顾自体软骨细胞移植技术的发展过程并对其未来方向作以简单设想。资料来源:应用计算机检索Medline1957-01/2005-09的文章,检索词为“autologous/autogeneouschondrocyteimplantation/transplantation,car-tilagedefect,ACI”,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1994-01/2005-09期间的相关文章,检索词“骨性关节炎、关节软骨剥脱、关节软骨缺损、关节软骨损伤、软骨细胞移植、自体软骨细胞移植”,限定文章语言种类为中文。另外在google搜索引擎及有关生物医学公司网站搜集相关资料。资料选择:纳入标准:①软骨细胞体外培养及移植的基础理论。②动物实验。③FDA审批文件。④临床应用报告。⑤患者随访分析。⑥自体软骨细胞移植技术与其他治疗方法疗效对比。排除标准:①较陈旧的文献。②重复研究。资料提炼:共收集到300余篇(页)与关节软骨损伤、缺损及其治疗相关的文献及网页,其中56篇(页)符合纳入标准,排除的240篇(页)文章系同一类重复性研究和近似的网络文章。资料综合:①软骨细胞的体外大规模培养技术和在动物体进行的软骨细胞移植实验为自体软骨细胞移植在人体的进一步研究奠定了理论基础。②初期的自体软骨细胞移植技术通过缝合自体骨膜来制造封闭关节软骨缺损病灶的空腔,再将体外培养扩增后的自体软骨细胞混悬液注射进入该空腔从而使细胞在病灶处形成新生软骨。③后发展为胶原膜被用来替代自体骨膜作为自体软骨细胞移植术中的病灶封闭材料。④近年来又研制出将体外培养扩增后的自体软骨细胞与Ⅰ/Ⅲ型胶原膜复合制成固态膜片,再将该膜用生物胶贴附在关节软骨缺损部位,移植的细胞以胶原膜为基质而增生,修复原软骨缺损。⑤基质诱导的自体软骨细胞移植技术还不是最完美的方案,仍然存在不足。因此需要向更安全、有效,更易于运输、保存及更低制造成本等方向研究。结论:经过10多年的不断改进,自体软骨细胞移植技术已经成为目前治疗关节软骨缺损的最佳方案,其新一代的基质诱导的自体软骨细胞移植技术应该得到临床普及来治疗这一疾病。

OBJECTIVE： In the past decade, autologous chondrocyte implantation （ACI） became the best answer to this question. This article was to clarify the evolving route of ACI and predict its coming improvements. DATA SOURCES： An online search of Medline database was undertaken to identify articles published in English between January 1957 to September 2005 by using the keywords of “autologous/autogeneous chondrocyte implantation/transplantation, cartilage defect, ACI”. Meanwhile, Chinese relevant articles published in English between January 1994 to September 2005 in China journal full-text database by using the keywords of “osteoarthritis, articular cartilage defect, articular cartilage injury, chondrocyte implantation/transplantation, autologous/autogeneous chondrocyte implantation/transplantation” in Chinese. Besides, some websites and webpages were also searched by Google. STUDY SELECTION： Inclusive criteria： ① basic theory about chondrocyte cultivation in vitro and implantation; ② animal experiments; ③FDA files; ④ report of clinical application; ⑤patients follow-up analysis; ⑥ comparison of ACI with other treatments. Exclusive criteria： ①too old literatures. ② Meta analysis, repeated study. DATA EXTRACTION： Totally more than 300 articles and webpages about the injury, defect and treatment of chondrocyte were collected, only 56 of them met the inclusive criteria, and the other 240 literatures were excluded due to repeated study and similar webpages. DATA SYNTHESIS： ① Techniques such as large scale cultivation of chondrocytes in vitro and chondrocyte transplantation tests on animal had lay a foundation for the further study of ACI on human body. ② In the primal ACI operations, autograft periosteum was sutured around the articular cartilage defect to seal it and make a cavity. Then suspension of chondrocytes, which had been cultivated and expanded in vitro, was injected into this cavity to deliver the chondrocytes and the later will become generate into new cartilage.③The collagen membrane was used to replace periosteum as the focal sealant for ACI.④Recently, new cultivated and expanded chondroeytes was combined into type Ⅰ/Ⅲ collagen membrane to make a flap, then it was pasted down to the floor of chondral defect with biodegradable glue. Implanted chondroeytes depend on this collagen menrbrane as its matrix to generage and grow up, and repair the defect in the end. ⑤Matrix-induced autologous chondroeyte implantation （MACI） is not the perfect one, it still has its own disadvantage. Therefore it should be improved toward directions like safer and more effective, easy to store and trasport, and lower cost. CONCLUSION： After continual improvement of more than one decade, AC1 has become the best resolution for articular cartilage defect. Its new generation, MAC1 should be widely applied in clinic to heal this disease.