骨髓间充质干细胞关节腔注射治疗兔软骨缺损的最适浓度

文题释义： 骨髓间充质干细胞促进软骨再生修复：是一种具有多分化潜能的干细胞，能在分化成软骨细胞后保持一定的增殖能力，可通过归巢迁移至软骨损伤部位，抑制组织炎症，通过旁分泌功能传递信号分子，在软骨的再生修复中起到重要作用。 兔关节软骨缺损模型：兔是实验研究中常用小动物模型，且在小动物中兔具有较大的膝关节，有利于手术操作及结果观察。相比于猪、马、羊等大动物模型，兔模型具有实验周期短、更经济、易于操作及饲养等优点。 背景：骨髓间充质干细胞现已广泛用于动物实验及临床研究中，各研究所用的细胞浓度、治疗次数及研究结果存在明显差异，缺乏最适细胞浓度的标准。 目的：探讨骨髓间充质干细胞关节腔内注射治疗兔软骨缺损的最适细胞浓度。 方法：取6月龄雄性新西兰大白兔30只，按骨髓间充质干细胞关节腔注射浓度随机分为对照组、1×10⁸ L^-1，1×10⁹ L^-1，1×10¹⁰ L^-1，1×10¹¹ L^-1组。在大白兔双侧股骨滑车建立直径3.0 mm、深度2.0 mm的软骨缺损模型。建模成功1周后，对照组双侧膝关节腔内注射1 mL生理盐水，其他4组分别注射1 mL细胞浓度为1×    10⁸ L^-1，1×10⁹ L^-1，1×10¹⁰ L^-1，1×10¹¹ L^-1的骨髓间充质干细胞悬液。注射后6周及12周，大体观察股骨滑车标本，行苏木精-伊红染色、番红-O-固绿染色、Ⅰ型及Ⅱ型胶原免疫组化染色，评估软骨组织修复效果。 结果与结论：对照组术后缺损区域明显，软骨组织无明显再生；1×10⁸ L^-1，1×10⁹ L^-1，1×10¹⁰ L^-1组软骨缺损区域可见软骨组织再生，且修复效果随注射间充质干细胞浓度增加而增强。1×10¹¹ L^-1组软骨修复效果与1×10¹⁰ L^-1组相似(P > 0.05)。结果表明，1×10¹⁰ L^-1是骨髓间充质干细胞关节腔内注射治疗软骨缺损的最佳细胞浓度，浓度过高时并不能增强其修复效果。 ORCID: 0000-0002-4585-8321(陈钢泓) 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Intra-articular injection of optimal concentration of bone marrow mesenchymal stem cells for treating rabbit cartilage defects

BACKGROUND:Bone marrow mesenchymal stem cells have been extensively applied in animal experiments and clinical studies.The cell concentration,treatment times and results in each study are different,and there is no standard for optimal cell concentration.OBJECTIVE:To investigate the optimal concentration of bone mesenchymal stem cells injected into articular cavity in the treatment of rabbit cartilage defects.METHODS:Thirty 6-month-old New Zealand white rabbits were selected and randomly divided into control,1×10^8,1×10^9,1×10^10,and 1×10^11/L groups.Cartilage defect models with diameter of 3 mm and depth of 2 mm were established in femoral trochlea in each group.One week after modeling,1 mL of normal saline was injected into the rabbit’s knee of the control group.The other groups were injected with bone marrow mesenchymal stem cells at corresponding concentrations.After 6 and 12 weeks,gross observation,hematoxylin-eosin staining,Safranin-O-fast green-staining,type I and II collagen staining were performed to assess the cartilage regeneration.RESULTS AND CONCLUSION:In the control group,the defect area was obvious with no cartilage regeneration.The 1×10^8,1×10^9,and 1×10^10/L groups showed cartilage regeneration.The repairing effect was increased with the cell concentration increasing.The effect of cartilage repair in the 1×10^11/L group was similar to that in the 1×10^10/L group(P>0.05).Therefore,1×10^10/L is the optimal concentration for intra-articular injection of bone marrow mesenchymal stem cells for treating cartilage defects,and higher concentration cannot enhance the repairing effect.