Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, Colorado, USA.
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
J Orthop Res. 2023 Apr;41(4):902-912. doi: 10.1002/jor.25431. Epub 2022 Sep 13.
Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published. Therefore, the aim of this study was to evaluate the short-term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 10 adMSCs or vehicle control for 4 weeks in peripheral veins; harvest occurred 2 weeks after the final injection. Systemic administration of adMSCs resulted in no adverse effects and was efficacious in reducing clinical signs of OA (as assessed by computer-aided gait analysis) compared to control injected animals. Further, there were significant decreases in key inflammatory mediators (including monocyte chemoattractant protein-1, tumor necrosis factor, and prostaglandin E ) both systemically (liver, kidney, and serum) and locally in the knee (joint tissues and synovial fluid) in animals treated with IV adMSCs relative to controls (as per enzyme-linked immunosorbent assay and/or immunohistochemistry, dictated by tissue sample). Thus, systemic administration of adMSCs by IV injection significantly improved gait parameters and reduced both systemic and intra-articular inflammatory mediators in animals with OA. These findings demonstrate the potential utility of alternative delivery approaches for cellular therapy of OA, particularly for patients with multiple affected joints.
骨关节炎（OA）是老龄化人口中发病率较高的主要原因，但症状和/或疾病改善仍然难以捉摸。脂肪间充质基质细胞（adMSCs）具有免疫调节和抗炎特性，可减轻临床症状并中断疾病的发生和进展。事实上，已有多篇文献评估了关节内给予 adMSCs 的治疗作用；然而，发表的关于全身给药方法的评估相对较少。因此，本研究的目的是评估静脉内（IV）给予同种异体 adMSCs 在自发性 OA 模型中的短期影响，即哈特利豚鼠。患有中度 OA 的动物在周围静脉中每周接受一次 2×10 adMSCs 或载体对照注射，共 4 周；最后一次注射后 2 周进行收获。adMSCs 的全身给药没有不良反应，并能有效减轻 OA 的临床症状（通过计算机辅助步态分析评估），与接受对照注射的动物相比。此外，与对照组相比，经 IV adMSCs 治疗的动物的全身（肝脏、肾脏和血清）和局部（膝关节组织和滑液）关键炎症介质（包括单核细胞趋化蛋白-1、肿瘤坏死因子和前列腺素 E）均显著降低（根据酶联免疫吸附试验和/或免疫组织化学，由组织样本决定）。因此，通过 IV 注射给予 adMSCs 的全身给药可显著改善步态参数，并降低 OA 动物的全身和关节内炎症介质。这些发现表明，细胞治疗 OA 的替代给药方法具有潜在的应用价值，特别是对于多个受累关节的患者。
