State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, China.
Osteoarthritis Cartilage. 2011 Jun;19(6):743-50. doi: 10.1016/j.joca.2011.02.015. Epub 2011 Mar 12.
Articular cartilage of the mandibular condyle has limited ability to regenerate itself after injury. This study was to investigate whether osteochondral defects in mandibular condyle could be repaired by NELL-1(NEL-like molecule-1)-modified autogenous bone marrow mesenchymal stem cells (BMMSCs) and poly lactic-co-glycolic acid (PLGA) composite.
Osteochondral defects of 3mm-diameter × 5mm-depth were created unilaterally in the central part of the condyle in 50 adult goats. The injury sites were treated with NELL-1-modified BMMSCs/PLGA, BMMSCs/PLGA, PLGA alone, or left empty. The defect area was monitored using gross examination, histology, immunohistochemistry, and micro-computed tomography (μ-CT). Implanted BMMSCs were tracked using Adeno-LacZ labeling.
The NELL-1-modified BMMSCs/PLGA group showed vigorous and rapid repair leading to regeneration of fibrocartilage at 6 weeks and to complete repair of native articular cartilage and subchondral bone at 24 weeks. The BMMSCs/PLGA group also completely repaired the defect with fibrocartilage at 24 weeks, but the cartilage in the BMMSCs/PLGA group was less well-organized than the NELL-1-modified BMMSCs/PLGA. The osteochondral defects in the PLGA and empty defect groups were poorly repaired, and no cartilage in the empty defect group or only small portion of cartilage in the PLGA group was found. In vivo viability of implanted cells was demonstrated by the retention for 6 weeks in the defects.
These findings demonstrated that NELL-1-modified BMMSCs/PLGA composite can rapidly repair large osteochondral defect in the mandibular condyle with regeneration of native fibrocartilage and subchondral bone.
下颌骨髁突的关节软骨在受伤后自身再生能力有限。本研究旨在探讨 NELL-1(NEL 样分子 1)修饰的自体骨髓间充质干细胞(BMMSCs)和聚乳酸-共-羟基乙酸(PLGA)复合材料是否能修复下颌骨髁突的骨软骨缺损。
在 50 只成年山羊的髁突中央造成 3mm 直径×5mm 深度的骨软骨缺损。用 NELL-1 修饰的 BMMSCs/PLGA、BMMSCs/PLGA、PLGA 单独或不处理(空白)处理损伤部位。通过大体检查、组织学、免疫组织化学和微计算机断层扫描(μ-CT)监测缺损面积。使用 Adeno-LacZ 标记追踪植入的 BMMSCs。
NELL-1 修饰的 BMMSCs/PLGA 组在 6 周时表现出活跃而快速的修复,导致纤维软骨再生,在 24 周时完全修复了原生关节软骨和软骨下骨。BMMSCs/PLGA 组也在 24 周时完全修复了缺损,形成纤维软骨,但 BMMSCs/PLGA 组的软骨结构不如 NELL-1 修饰的 BMMSCs/PLGA 组有序。PLGA 和空白缺损组的骨软骨缺损修复不良,空白缺损组无软骨,PLGA 组仅有小部分软骨。体内植入细胞的存活能力通过在缺陷部位保留 6 周得到证实。
这些发现表明,NELL-1 修饰的 BMMSCs/PLGA 复合材料能快速修复下颌骨髁突的大骨软骨缺损,再生原生纤维软骨和软骨下骨。