Experimental Trauma Surgery, Department of Trauma Surgery, University Medical Center Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany.
Sporthopaedicum Regensburg, Hildegard von Bingen Strasse 1, 93053, Regensburg, Germany.
Stem Cell Res Ther. 2017 Oct 10;8(1):225. doi: 10.1186/s13287-017-0678-z.
Treatment of meniscus tears within the avascular region represents a significant challenge, particularly in a situation of early osteoarthritis. Cell-based tissue engineering approaches have shown promising results. However, studies have not found a consensus on the appropriate autologous cell source in a clinical situation, specifically in a challenging degenerative environment. The present study sought to evaluate the appropriate cell source for autologous meniscal repair in a demanding setting of early osteoarthritis.
A rabbit model was used to test autologous meniscal repair. Bone marrow and medial menisci were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen-hyaluronan scaffolds before implantation. A punch defect model was performed on the lateral meniscus and then a cell-seeded scaffold was press-fit into the defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were assessed, and menisci were harvested for macroscopic, histological, and immunohistochemical evaluation using a validated meniscus scoring system. In conjunction, human meniscal cells isolated from non-repairable bucket handle tears and human MSCs were expanded and, using the pellet culture model, assessed for their meniscus-like potential in a translational setting through collagen type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay (ELISA), and gene expression analysis.
After resections of the medial menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1). However, successful repair of meniscus punch defects was performed using either meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity for meniscal cell treatment. Furthermore, human MSCs had significantly increased collagen type II gene expression and production compared to meniscal cells (p < 0.05).
The regenerative potential of the meniscus by an autologous cell-based tissue engineering approach was shown even in a challenging setting of early osteoarthritis. Autologous MSCs and meniscal cells were found to have improved meniscal healing in an animal model, thus demonstrating their feasibility in a clinical setting. However, donor site morbidity, reduced availability, and reduced chondrogenic differentiation of human meniscal cells from debris of meniscal tears favors autologous MSCs for clinical use for cell-based meniscus regeneration.
治疗无血管区的半月板撕裂是一项重大挑战，尤其是在早期骨关节炎的情况下。基于细胞的组织工程方法已经显示出了良好的效果。然而，在临床情况下，特别是在具有挑战性的退行性环境中，尚未就合适的自体细胞来源达成共识。本研究旨在评估在早期骨关节炎的苛刻环境下进行自体半月板修复的合适细胞来源。
使用兔模型来测试自体半月板修复。在手术前 4 周采集骨髓和内侧半月板。分离、扩增骨髓间充质干细胞（MSCs）和半月板细胞，并在植入前将其接种到胶原-透明质酸支架上。在外侧半月板上进行穿孔缺陷模型，然后将细胞接种的支架压入缺陷中。6 或 12 周后，评估关节大体形态和 OARSI 分级，并采集半月板进行宏观、组织学和免疫组织化学评估，使用经过验证的半月板评分系统。同时，从不可修复的桶柄撕裂的人半月板细胞和人 MSCs 中分离出来并进行扩增，并在翻译环境中使用微球培养模型通过胶原 I 和 II 免疫染色、胶原 II 酶联免疫吸附测定（ELISA）和基因表达分析评估其半月板样潜能。
内侧半月板切除后，所有膝关节均出现早期骨关节炎改变（平均 OARSI 分级 3.1）。然而，使用半月板细胞或 MSCs 均可成功修复半月板穿孔缺陷。关节大体评估显示半月板细胞治疗存在供体部位发病率。此外，与半月板细胞相比，人 MSCs 显著增加了胶原 II 基因表达和产生（p < 0.05）。
即使在早期骨关节炎的挑战性环境下，基于自体细胞的组织工程方法也显示出了半月板的再生潜力。在动物模型中，发现自体 MSCs 和半月板细胞改善了半月板愈合，从而证明了它们在临床环境中的可行性。然而，供体部位发病率高、可用性降低以及半月板撕裂碎片来源的人半月板细胞的软骨形成分化能力降低，支持将自体 MSCs 用于临床应用，以进行基于细胞的半月板再生。
