【骨关节炎】鼻子，不单单只是好看了，也有其他用处了！

鼻中隔软骨组织工程法构建自体软骨组织治疗关节软骨损伤的观察性试验

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial浙江大学医学院附属第二医院骨科沈炜亮

Marcus Mumme, Andrea Barbero(巴塞尔大学医学院)

Lancet, 2016.10.22

关节软骨损伤修复能力差，常导致进行性的关节病变，且不能被常规治疗或者关节软骨细胞移植的先进疗法治愈。与关节软骨细胞移植相比，鼻中隔软骨细胞具有更强的生成透明软骨组织的能力，更强的适应关节内的环境的可塑性。我们旨在评估鼻中隔软骨细胞形成软骨组织自体移植治疗膝关节软骨损伤的安全性和功能恢复情况。

图1 患者一般情况

选取10例在瑞士巴塞尔大学医学院接受治疗的由外伤造成的股骨髁和滑车关节全层软骨病变（2-6m2）的有症状的患者，在6 mm的鼻中隔软骨活检标本中分离软骨细胞，并培养增殖在胶原膜上形成软骨组织，利用关节切开术将其植入到缺损处，术后1年进行评估。主要的结局指标是可行性和安全性。次要指标是自我症状评分和MRI影像学检测修复组织的形态和组成成分。

图2 临床症状评分

对每位病人而言，在富含黏多糖和II型胶原蛋白的细胞外基质中培养鼻软骨细胞形成软骨组织移植是可行的，软骨组织可稳定嵌入到关节损伤处。术后1年无不良反应且自我临床疼痛评分、膝关节功能和生活质量具有明显改善。影像学检测表明不同程度的软骨缺损修复都接近于正常软骨。

图3 MRI检测结果

自体鼻中隔软骨细胞形成透明软骨组织可用于临床上膝关节软骨缺损的修复。未来的研究有必要在大型对照试验中评估疗效，并延伸调查早期退行性状态或其他关节适应症。

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects.

In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2–6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via miniarthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients.

For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months

after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage.

Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints.

整理者/作者：沈炜亮

浙江大学医学院附属第二医院·骨科；

浙江大学骨科研究所；

浙江大学李达三·叶耀珍再生医学发展基金；

浙江省组织工程与再生医学技术重点实验室；

中国医师协会骨科医师分会再生医学工作组；

本人专业诊治范围：

1，肌腱病&肌腱/韧带损伤：肘-网球肘；肩-肩周炎，肩袖损伤；膝-弹跳膝，跑步者膝，前交叉韧带损伤；踝-跟腱炎，跟腱断裂；手腕部-腱鞘炎；筋膜炎

2，再生医学技术治疗运动系统疑难杂症，包括：软骨/半月板/肌腱/韧带的修复、重建和再生；

门诊类型：肌腱病专科门诊！

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