Human Adipose-derived Stem Cells Upregulate IGF-1 and Alleviate Osteoarthritis in a Two-stage Rabbit Osteoarthritis Model.

Juan Wang, Shibo Su, Chuanming Dong, Qiang Fan, Jishu Sun, Siqing Liang, Zuhuo Qin, Chuqing Ma, Jianfeng Jin, Hongwen Zhu, Tongmeng Jiang, Jun Xu
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Abstract

Objective: In recent years, it has been known that mesenchymal stem cells (MSCs) have the potential to treat osteoarthritis (OA). This study aimed to investigate the effects of intraarticular injection of human adipose-derived stem cells (hADSCs) in a new double-damage rabbit osteoarthritis model.

Methods: The OA model was established surgically first by medial collateral ligament and anterior insertional ligament transection and medical meniscectomy, then by articular cartilage full-thickness defect. At six weeks following surgery, hADSCs were labeled with Enhanced Green Fluorescence Protein expressing lentivirus FG12 and injected into the knee joints. All rabbits were sacrificed at 4- and 8 weeks post-surgery. Assessments were carried out by macroscopic examination, immunohistochemistry staining, magnetic resonance imaging, qRT-PCR and ELISA analysis.

Results: At 4- and 8 weeks, hADSCs injection showed less cartilage loss, few fissures and few cracks, decreased volume of joint effusion and cartilage defect measured with MRI. Furthermore, ELISA and qRT-PCR methods showed that hADSCs treatment increased the level of IGF-1.

Conclusions: Our data suggest that hADSC transplantation promotes articular cartilage healing in the double-damage rabbit osteoarthritis model, IGF-1 may play an essential role in the hADSC-based cartilage repair process. Transplantation of hADSCs may be suitable for clinical application in the treatment of osteoarthritis.

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人脂肪干细胞在两阶段家兔骨关节炎模型中上调 IGF-1 并缓解骨关节炎。
目的:近年来,人们已经知道间充质干细胞(MSCs)具有治疗骨关节炎(OA)的潜力。本研究旨在探讨在新的双重损伤兔骨关节炎模型中关节内注射人脂肪来源干细胞(hADSCs)的效果:首先通过内侧副韧带、前插入韧带横断和内科半月板切除术建立OA模型,然后进行关节软骨全厚缺损。术后六周,用表达慢病毒 FG12 的增强型绿色荧光蛋白标记 hADSCs 并将其注入膝关节。所有兔子分别于术后4周和8周处死。评估方法包括宏观检查、免疫组化染色、磁共振成像、qRT-PCR 和 ELISA 分析:结果:注射 hADSCs 4 周和 8 周后,软骨损失较少,裂缝和裂纹较少,关节积液量减少,核磁共振成像显示软骨缺损。此外,ELISA和qRT-PCR方法显示,hADSCs治疗可提高IGF-1的水平:我们的数据表明,hADSCs移植可促进双重损伤兔骨关节炎模型的关节软骨愈合,IGF-1可能在以hADSCs为基础的软骨修复过程中发挥了重要作用。hADSCs移植可能适合用于骨关节炎的临床治疗。
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