The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.
The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.
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DOI：
10.1186/s13018-017-0534-y
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发表时间：
2017-03-09
影响因子：
2.6
通讯作者：
Zaidi R
中科院分区：
文献类型：
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作者：
Goldberg A;Mitchell K;Soans J;Kim L;Zaidi R
由于关节软骨的无血管、无神经和无淋巴的特性，关节软骨缺损的治疗在临床上存在诸多挑战。骨髓刺激技术，如微骨折术，是临床实践中最常用的方法，然而由此产生的混合纤维软骨组织不如天然透明软骨。其他方法已显示出有希望，但远非完美。对于需要软骨修复的患者，再生医学和组织工程方面存在未满足的需求且人们的兴趣日益增加。许多已发表的关于软骨修复的综述仅列举人体临床试验，低估了作为未来研究先导的大量基础科学和动物研究。因此，我们着手对文献进行系统综述，以评估干细胞疗法的转化情况，探究在从实验室（体外）、动物（临床前）到人体研究（临床）的各个转化阶段进行了哪些研究，并为负责任地将干细胞疗法引入软骨缺损治疗构建一个基于证据的级联。
本综述依据PRISMA指南，使用1900年1月1日至2015年6月30日的CINHAL、MEDLINE、EMBASE、Scopus和Web of Knowledge数据库进行。总共确定了2880项研究，其中252项研究被纳入分析（100篇体外研究文章，111项动物研究；31项人体研究）。临床前研究在细胞来源方面存在巨大差异，包括所用动物、采集部位（脂肪、骨髓、血液或滑膜）以及同种异体性等方面。支架的使用、生长因子、细胞传代次数和所用细胞数量也存在极大的异质性。
本综述对基础科学向软骨修复临床实践转化背后的证据进行了全面评估。它揭示了体外、临床前和人体数据之间缺乏关联性，以及协同证据的拼凑情况。这一领域的进展动力在很大程度上由患者需求、外科医生的探究以及与新进展同步学习的监管框架所驱动。
The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place.