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Role of growth factors in rabbit articular cartilage repair by chondrocytes in agarose.

机译:生长因子在琼脂糖中软骨细胞修复兔关节软骨中的作用。

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OBJECTIVE: Novel approaches to intervention in joint diseases consist of the replacement of diseased cartilage by in vitro engineered, viable cells or graft tissues. Two major obstacles remain to be overcome: (1) Hyaline cartilage in vitro often loses differentiated traits. (2) Grafts frequently are not integrated satisfactorily into host cartilage and/or the tissue is remodelled in situ into functionally inferior fibrocartilage. Therefore, we have explored the possibility whether chondrocytes embedded into agarose gels provided better graft tissues in a repair model of full thickness defects in rabbit joint cartilage. DESIGN: Experimental defects of knee joint cartilage was filled with articular chondrocytes cultured in agarose gels. Chondrocytes in vitro either remained unstimulated or were treated with several growth factors. Repair of the defects was assessed by histology and was scored between 0 (no healing) and 1 (perfect healing) as judged by the follwing parameters: intensity of proteoglycan staining, organization of the superficial zone, ossification at the border between repair cartilage and subchondral bone, tidemark formation in the repaired area, arrangement of chondrocytes, and integration of repair cartilage into host. RESULTS: Treatment of chondrocyte cultures with bFGF had a stabilizing effect on the differentiated state of the cells in implanted grafts whereas bone morphogenetic proteins stimulated ingrowth of subchondral bone reducing repair cartilage thickness and preventing normal tide mark formation; TGF-beta did not significantly affect evaluation parameters in comparison with untreated controls. CONCLUSION: Growth factor treatment resulted in an ambiguous quality of graft development. Only FGF had a clear beneficial effect to the graft tissues after 1 month. Further studies are required to define the precise conditions and sequence of growth factor treatment of in vitro engineered cartilage which benefits graft quality.
机译:目的:干预关节疾病的新方法包括用体外改造的活细胞或移植组织代替患病的软骨。有两个主要障碍有待克服:(1)体外透明软骨通常会失去分化的特征。 (2)移植物经常不能令人满意地整合到宿主软骨中和/或组织被原位重塑为功能性下纤维软骨。因此,我们探索了在兔关节软骨全层缺损修复模型中,琼脂糖凝胶中嵌入的软骨细胞是否提供了更好的移植组织的可能性。设计:用琼脂糖凝胶培养的关节软骨细胞填充膝关节软骨的实验缺陷。体外软骨细胞未受刺激或已用几种生长因子处理。通过组织学评估缺损的修复情况,并根据以下参数判断其得分为0(无愈合)和1(完全愈合):蛋白聚糖染色强度,浅表区域的组织,修复软骨和软骨下边界的骨化骨骼,修复部位潮汐形成,软骨细胞排列以及修复软骨整合入宿主。结果:用bFGF处理软骨细胞可稳定植入移植物中细胞的分化状态,而骨形态发生蛋白可刺激软骨下骨向内生长,从而减少修复软骨的厚度并阻止正常的潮痕形成。与未处理的对照组相比,TGF-β并未显着影响评估参数。结论:生长因子治疗导致移植物发育质量模糊。 1个月后,仅FGF对移植物组织具有明显的有益作用。需要进一步的研究来确定生长因子处理体外工程化软骨的确切条件和顺序,这将有利于移植物质量。

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