Smeriglio Piera, Dhulipala Lakshmi, Lai Janice H, Goodman Stuart B, Dragoo Jason L, Smith Robert L, Maloney William J, Yang Fan, Bhutani Nidhi
1 Department of Orthopedic Surgery, Stanford University , Stanford, California.
Tissue Eng Part A. 2015 Feb;21(3-4):840-9. doi: 10.1089/ten.TEA.2014.0375. Epub 2014 Nov 11.
Regeneration of human cartilage is inherently inefficient. Current cell-based approaches for cartilage repair, including autologous chondrocytes, are limited by the paucity of cells, associated donor site morbidity, and generation of functionally inferior fibrocartilage rather than articular cartilage. Upon investigating the role of collagen VI (Col VI), a major component of the chondrocyte pericellular matrix (PCM), we observe that soluble Col VI stimulates chondrocyte proliferation. Interestingly, both adult and osteoarthritis chondrocytes respond to soluble Col VI in a similar manner. The proliferative effect is, however, strictly due to the soluble Col VI as no proliferation is observed upon exposure of chondrocytes to immobilized Col VI. Upon short Col VI treatment in 2D monolayer culture, chondrocytes maintain high expression of characteristic chondrocyte markers like Col2a1, agc, and Sox9 whereas the expression of the fibrocartilage marker Collagen I (Col I) and of the hypertrophy marker Collagen X (Col X) is minimal. Additionally, Col VI-expanded chondrocytes show a similar potential to untreated chondrocytes in engineering cartilage in 3D biomimetic hydrogel constructs. Our study has, therefore, identified soluble Col VI as a biologic that can be useful for the expansion and utilization of scarce sources of chondrocytes, potentially for autologous chondrocyte implantation. Additionally, our results underscore the importance of further investigating the changes in chondrocyte PCM with age and disease and the subsequent effects on chondrocyte growth and function.
人类软骨的再生本质上效率低下。目前基于细胞的软骨修复方法，包括自体软骨细胞，受到细胞数量稀少、相关供体部位发病率以及生成功能较差的纤维软骨而非关节软骨的限制。在研究软骨细胞周细胞基质（PCM）的主要成分胶原蛋白VI（Col VI）的作用时，我们观察到可溶性Col VI能刺激软骨细胞增殖。有趣的是，成年软骨细胞和骨关节炎软骨细胞对可溶性Col VI的反应方式相似。然而，增殖效应严格归因于可溶性Col VI，因为当软骨细胞暴露于固定化Col VI时未观察到增殖现象。在二维单层培养中进行短时间Col VI处理后，软骨细胞维持如Col2a1、聚集蛋白聚糖（agc）和Sox9等特征性软骨细胞标志物的高表达，而纤维软骨标志物胶原蛋白I（Col I）和肥大标志物胶原蛋白X（Col X）的表达则极少。此外，在三维仿生水凝胶构建物中构建软骨时，经Col VI扩增的软骨细胞显示出与未处理软骨细胞相似的潜力。因此，我们的研究确定了可溶性Col VI作为一种生物制剂，可用于扩增和利用稀缺的软骨细胞来源，可能用于自体软骨细胞植入。此外，我们的结果强调了进一步研究软骨细胞PCM随年龄和疾病的变化及其对软骨细胞生长和功能的后续影响的重要性。
