Weisser J, Rahfoth B, Timmermann A, Aigner T, Bräuer R, von der Mark K
Institute of Pathology, University of Jena, Germany.
Osteoarthritis Cartilage. 2001;9 Suppl A:S48-54. doi: 10.1053/joca.2001.0444.
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.
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.
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.
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.
关节疾病的新型干预方法包括用体外工程化的活细胞或移植组织替代病变软骨。仍有两个主要障碍有待克服：（1）体外透明软骨常失去分化特性。（2）移植物通常不能令人满意地整合到宿主软骨中，和/或组织在原位重塑为功能较差的纤维软骨。因此，我们探讨了在兔关节软骨全层缺损修复模型中，嵌入琼脂糖凝胶的软骨细胞是否能提供更好的移植组织。
用在琼脂糖凝胶中培养的关节软骨细胞填充膝关节软骨的实验性缺损。体外软骨细胞要么不接受刺激，要么用几种生长因子处理。通过组织学评估缺损的修复情况，并根据以下参数在0（无愈合）至1（完美愈合）之间评分：蛋白聚糖染色强度、表层区域的组织结构、修复软骨与软骨下骨边界处的骨化、修复区域的潮标形成、软骨细胞的排列以及修复软骨与宿主的整合情况。
用碱性成纤维细胞生长因子（bFGF）处理软骨细胞培养物对植入移植物中细胞的分化状态有稳定作用，而骨形态发生蛋白刺激软骨下骨长入，减少修复软骨厚度并阻止正常潮标形成；与未处理的对照组相比，转化生长因子-β（TGF-β）对评估参数没有显著影响。
生长因子处理导致移植物发育质量参差不齐。1个月后只有成纤维细胞生长因子（FGF）对移植组织有明显的有益作用。需要进一步研究来确定有利于移植物质量的体外工程化软骨生长因子处理的精确条件和顺序。
