University of Iowa, Iowa City.
Arthritis Rheumatol. 2015 May;67(5):1274-85. doi: 10.1002/art.39049.
Articular cartilage damage after joint trauma seldom heals and often leads to osteoarthritis. We previously identified a migratory chondrogenic progenitor cell (CPC) population that responds chemotactically to cell death and rapidly repopulates the injured cartilage matrix, which suggests a potential approach for articular cartilage repair. This study was undertaken to determine whether recombinant human stromal cell-derived factor 1α (rhSDF-1α), a potent CPC chemoattractant, would improve the quality of cartilage regeneration, hypothesizing that increased recruitment of CPCs by rhSDF-1α would promote the formation of cartilage matrix upon chondrogenic induction.
Full-thickness bovine chondral defects were filled with hydrogel, composed of fibrin and hyaluronic acid and containing rhSDF-1α. Cell migration was monitored, followed by chondrogenic induction. Regenerated tissue was evaluated by histology, immunohistochemistry, and scanning electron microscopy. Push-out tests and unconfined compression tests were performed to assess the strength of tissue integration and the mechanical properties of the regenerated cartilage.
Use of rhSDF-1α dramatically improved CPC recruitment to the chondral defects at 12 days. After 6 weeks under chondrogenic conditions, cell morphology, proteoglycan density, and the ultrastructure of the repair tissue were all similar to that found in native cartilage. Compared with empty controls, neocartilage generated in rhSDF-1α-containing defects showed significantly greater interfacial strength, and acquired mechanical properties comparable to those of native cartilage.
This study showed that stimulating local CPC recruitment prior to treatment with chondrogenic factors significantly improves the biochemical and mechanical properties of the cartilage tissue formed in chondral defects. This simple approach may be implemented in vivo as a one-step procedure by staging the release of chemokine and chondrogenic factors from within the hydrogel, which can be achieved using smart drug-delivery systems.
关节创伤后的关节软骨损伤很少愈合，常导致骨关节炎。我们之前发现了一种迁移性软骨祖细胞（CPC）群体，它对细胞死亡有趋化反应，并迅速重新填充受伤的软骨基质，这表明了一种潜在的关节软骨修复方法。本研究旨在确定重组人基质细胞衍生因子 1α（rhSDF-1α）是否会提高软骨再生的质量，假设 rhSDF-1α 增加 CPC 的募集将促进软骨诱导时软骨基质的形成。
全层牛软骨缺损用纤维蛋白和透明质酸组成的水凝胶填充，并含有 rhSDF-1α。监测细胞迁移，然后进行软骨诱导。通过组织学、免疫组织化学和扫描电子显微镜评估再生组织。进行推挤试验和无约束压缩试验，以评估组织整合强度和再生软骨的机械性能。
使用 rhSDF-1α 可显著改善 CPC 在 12 天内对软骨缺损的募集。在软骨形成条件下 6 周后，细胞形态、糖胺聚糖密度和修复组织的超微结构均与天然软骨相似。与空载体对照组相比，rhSDF-1α 存在的缺陷中产生的新生软骨具有显著更高的界面强度，并获得了与天然软骨相当的机械性能。
本研究表明，在使用软骨形成因子治疗之前刺激局部 CPC 募集可显著改善软骨缺损中形成的软骨组织的生化和机械性能。这种简单的方法可以通过从水凝胶内分期释放趋化因子和软骨形成因子来在体内实现，这可以通过智能药物输送系统来实现。
