Yan Wenqiang, Maimaitimin Maihemuti, Zhao Fengyuan, Fan Yifei, Yang Shuai, Li Yuwan, Cao Chenxi, Shao Zhenxing, Liu Ziming, Hu Xiaoqing, Ao Yingfang, Cheng Jin
Department of Sports Medicine, Peking University Third Hospital, China.
Institute of Sports Medicine of Peking University, China.
J Orthop Translat. 2022 Mar 4;33:72-89. doi: 10.1016/j.jot.2022.02.004. eCollection 2022 Mar.
Synovium has been confirmed to be the primary contributor to meniscal repair. Particulated Juvenile Allograft Cartilage (PJAC) has demonstrated promising clinical effect on repairing cartilage. The synergistic effect of synovium and PJAC transplant on meniscal fibrocartilaginous repair is unclear. We hypothesize that the transplantation of synovium and PJAC synergistically facilitates meniscal regeneration and the donor cells within graft tissues still survive in the regenerated tissue at the last follow up (16 weeks postoperatively).
The study included 24 mature female rabbits, which were randomly divided into experimental and control groups. A cylindrical full-thickness defect measuring 2.0 mm was prepared in the avascular portion of the anterior horn of medial meniscus in both knees. The synovium and PJAC transplant were harvested from juvenile male rabbits (2 months after birth). The experimental group received synovium and PJAC transplant encapsulated with fibrin gel. The control groups received synovium transplant encapsulated with fibrin gel, pure fibrin gel and nothing. The macroscopic, imageological and histological evaluations of repaired tissue were performed at 8 weeks and 16 weeks postoperatively. The in situ hybridization (ISH) of male-specific sex-determining region Y-linked (SRY) gene was performed to detect the transplanted cells.
The regenerated tissue in experimental group showed superior structural integrity, superficial smoothness, and marginal integration compared to control groups at 8 weeks or 16 weeks postoperatively. More meniscus-like fibrochondrocytes filled the repaired tissue in the experimental group, and the matrix surrounding these cell clusters demonstrated strongly positive safranin O and type 2 collagen immunohistochemistry staining. By SRY gene ISH, the positive SRY signal of experimental group could be detected at 8 weeks (75.72%, median) and 16 weeks (48.69%, median). The expression of SOX9 in experimental group was the most robust, with median positive rates of 65.52% at 8 weeks and 67.55% at 16 weeks.
The transplantation of synovium and PJAC synergistically facilitates meniscal regeneration. The donor cells survive for at least 16 weeks in the recipient.
This study highlighted the positive effect of PJAC and synovium transplant on meniscal repair. We also clarified the potential repair mechanisms reflected by the survival of donor cells and upregulated expression of meniscal fibrochondrocytes related genes. Thus, based on our study, further clinical experiments are needed to investigate synovium and PJAC transplant as a possible treatment to meniscal defects.
滑膜已被证实是半月板修复的主要贡献者。颗粒状幼年同种异体软骨（PJAC）在软骨修复方面已显示出有前景的临床效果。滑膜和PJAC移植对半月板纤维软骨修复的协同作用尚不清楚。我们假设滑膜和PJAC移植协同促进半月板再生，并且移植组织中的供体细胞在最后一次随访（术后16周）时仍存活于再生组织中。
本研究纳入24只成年雌性兔子，随机分为实验组和对照组。在双膝内侧半月板前角的无血管部分制备一个直径2.0毫米的圆柱形全层缺损。滑膜和PJAC移植组织取自幼年雄性兔子（出生后2个月）。实验组接受用纤维蛋白凝胶包裹的滑膜和PJAC移植。对照组分别接受用纤维蛋白凝胶包裹的滑膜移植、单纯纤维蛋白凝胶和不做处理。在术后8周和16周对修复组织进行宏观、影像学和组织学评估。进行雄性特异性Y染色体性别决定区（SRY）基因的原位杂交（ISH）以检测移植细胞。
与对照组相比，术后8周或16周时，实验组的再生组织在结构完整性、表面光滑度和边缘整合方面表现更优。实验组有更多半月板样纤维软骨细胞填充修复组织，这些细胞簇周围的基质在番红O染色和Ⅱ型胶原免疫组化染色中呈强阳性。通过SRY基因ISH检测，实验组在8周（中位数为75.72%）和16周（中位数为48.69%）时可检测到阳性SRY信号。实验组中SOX9的表达最为显著，8周时阳性率中位数为65.52%，16周时为67.55%。
滑膜和PJAC移植协同促进半月板再生。供体细胞在受体中存活至少16周。
本研究突出了PJAC和滑膜移植对半月板修复的积极作用。我们还阐明了供体细胞存活和半月板纤维软骨细胞相关基因表达上调所反映的潜在修复机制。因此，基于我们的研究，需要进一步的临床实验来研究滑膜和PJAC移植作为半月板缺损可能治疗方法的可行性。
