Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs
Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs
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DOI：
10.1177/0363546519859855
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发表时间：
2019-07-15
影响因子：
4.8
通讯作者：
Sekiya, Ichiro
中科院分区：
文献类型：
--
作者：
Kondo, Shimpei;Nakagawa, Yusuke;Sekiya, Ichiro
背景资料：先前的工作已经证明，膝关节软骨缺损的患者从关节镜下移植自体滑膜间充质干细胞（MSC）的磁共振成像（MRI），定性组织学检查结果和Lysholm评分方面受益。然而，有效性受到所获得的单元数量的限制，因此未研究大尺寸缺陷（>500 mm（2））。MSC聚集体的使用可以通过增加粘附于软骨缺损的MSC的数量来治疗较大的缺损。目的：探讨自体滑膜间充质干细胞聚集体二步手术移植是否能促进微型猪骨软骨缺损关节软骨再生。研究设计：对照实验室研究。方法：体外培养小型猪滑膜间充质干细胞，观察其集落形成能力和多向分化能力。用悬滴培养物形成250，000个滑膜MSC的聚集体，并将16个聚集体（对于每个缺损）植入在内侧股骨髁和股骨沟中产生的两个骨软骨缺损（6 × 6 × 1.5 mm）上（MSC组）。对侧膝关节的缺损为空（对照组）。在第4周和第12周通过肉眼观察和组织学检查对膝关节进行评价。在12周时获得MRI T1rho标测图像。为了进行细胞追踪，在聚集体形成之前用ferucarbotran标记滑膜MSC，并在1周时用MRI观察。结果：滑膜间充质干细胞具有体外集落形成和多向分化能力。MSC组的再生软骨形成明显优于对照组，如12周时内侧髁的国际软骨修复学会评分（宏观）、改良Wakitani评分（组织学）和T1rho标测（生化MRI）所示。1周时MRI观察到骨软骨缺损处植入的细胞，标记有阿魏酸。4周时内侧髁的改良Wakitani评分与4周和12周时股骨沟的改良Wakitani评分无显著差异。结论：自体滑膜MSC聚集体移植促进了12周时微型猪股骨内侧髁关节软骨再生。
Background: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm(2)) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. Purpose: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. Study Design: Controlled laboratory study. Methods: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 x 6 x 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. Results: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. Conclusion: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs.