Department of Biomedical Science, CHA University, Seongnam, South Korea.
School of Integrative Engineering, Chung-Ang University, Seoul, South Korea.
J Tissue Eng Regen Med. 2018 Mar;12(3):667-675. doi: 10.1002/term.2485. Epub 2017 Oct 2.
Matrilin-3 is an essential extracellular matrix component present only in cartilaginous tissues. Matrilin-3 exerts chondroprotective effects by regulating an anti-inflammatory function and extracellular matrix components. We hypothesized that the codelivery of matrilin-3 with infrapatellar adipose-tissue-derived mesenchymal stem cells (Ad-MSCs) may enhance articular cartilage regeneration. Matrilin-3 treatment of Ad-MSCs in serum-free media induced collagen II and aggrecan expression, and matrilin-3 in chondrogenic media also enhanced in vitro chondrogenic differentiation. Next, the in vivo effect of matrilin-3 codelivery with Ad-MSCs on cartilage regeneration was assessed in an osteochondral defect model in Sprague Dawley rats: Ad-MSCs and hyaluronic acid were implanted at the defect site with or without matrilin-3 (140, 280, and 700 ng). Safranin O staining revealed that matrilin-3 (140 and 280 ng) treatment significantly improved cartilage regeneration and glycosaminoglycan accumulation. In the animals treated with 140-ng matrilin-3, in particular, the defect site exhibited complete integration with surrounding tissue and a smooth glistening surface. The International Cartilage Repair Society macroscopic and O'Driscoll microscopic scores for regenerated cartilage were furthermore shown to be considerably higher for this group (matrilin-3; 140 ng) compared with the other groups. Furthermore, the defects treated with 140-ng matrilin-3 revealed significant hyaline-like cartilage regeneration in the osteochondral defect model; in contrast, the defects treated with 700-ng matrilin-3 exhibited drastically reduced cartilage regeneration with mixed hyaline-fibrocartilage morphology. Codelivery of matrilin-3 with Ad-MSCs significantly influenced articular cartilage regeneration, supporting the potential use of this tissue-specific protein for a cartilage-targeted stem cell therapy.
基质连接蛋白-3 是一种仅存在于软骨组织中的重要细胞外基质成分。基质连接蛋白-3 通过调节抗炎功能和细胞外基质成分发挥软骨保护作用。我们假设与髌下脂肪组织来源间充质干细胞（Ad-MSCs）共递送基质连接蛋白-3 可能增强关节软骨再生。在无血清培养基中，基质连接蛋白-3 处理 Ad-MSCs 可诱导胶原 II 和聚集蛋白聚糖表达，软骨形成培养基中的基质连接蛋白-3 也可增强体外软骨分化。接下来，在 Sprague Dawley 大鼠的骨软骨缺损模型中评估了与 Ad-MSCs 共递送基质连接蛋白-3 对软骨再生的体内影响：在缺损部位植入 Ad-MSCs 和透明质酸，同时或不同时添加基质连接蛋白-3（140、280 和 700ng）。番红 O 染色显示，基质连接蛋白-3（140 和 280ng）处理可显著改善软骨再生和糖胺聚糖积累。特别是在用 140ng 基质连接蛋白-3 处理的动物中，缺损部位与周围组织完全整合，表面光滑有光泽。再生软骨的国际软骨修复学会宏观和 O'Driscoll 微观评分显示，该组（基质连接蛋白-3；140ng）明显高于其他组。此外，在骨软骨缺损模型中，用 140ng 基质连接蛋白-3 处理的缺陷部位显示出明显的透明样软骨再生；相比之下，用 700ng 基质连接蛋白-3 处理的缺陷部位软骨再生明显减少，表现为透明样纤维软骨形态。与 Ad-MSCs 共递送基质连接蛋白-3 显著影响关节软骨再生，支持将这种组织特异性蛋白用于针对软骨的干细胞治疗。
