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 × 10⁶ 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 E₂) 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.

中文翻译：

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静脉注射脂肪来源的间充质基质细胞有益于自发性骨关节炎模型的步态和炎症

骨关节炎 (OA) 是老龄化人群发病的主要原因，但症状和/或疾病改善仍然难以捉摸。脂肪来源的间充质基质细胞 (adMSC) 已证明具有免疫调节和抗炎特性，可以减轻临床症状并阻止疾病的发作和进展。事实上，许多手稿已经评估了 adMSCs 的关节内给药作为一种治疗方法；然而，对系统性交付方法的评估相对较少。因此，本研究的目的是评估在已建立的自发性 OA 模型 Hartley 豚鼠中静脉内 (IV) 递送同种异体 adMSC 的短期影响。中度骨关节炎动物每周注射一次 2 × 10 ⁶adMSCs 或载体对照外周静脉 4 周；收获发生在最后一次注射后 2 周。与对照注射动物相比，adMSCs 的全身给药没有产生不良反应，并且可有效减少 OA 的临床症状（通过计算机辅助步态分析评估）。此外，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 _{2 ）显着减少}) 全身（肝脏、肾脏和血清）和膝关节（关节组织和滑液）局部（关节组织和滑液）在接受 IV adMSCs 治疗的动物中相对于对照组（根据酶联免疫吸附测定和/或免疫组织化学，由组织样本决定） . 因此，通过 IV 注射全身施用 adMSC 可显着改善 OA 动物的步态参数并减少全身和关节内炎症介质。这些发现证明了替代递送方法对 OA 细胞治疗的潜在效用，特别是对于具有多个受影响关节的患者。