Department of Biomedical Engineering, Rensselaer Polytechnic Institute , Troy, New York.
Tissue Eng Part A. 2018 Sep;24(17-18):1390-1392. doi: 10.1089/ten.TEA.2017.0390. Epub 2018 Jun 4.
The long-term goal of this work is to develop a potassium (K)-based intra-articular (IA) injection for osteoarthritis treatment. Within this context, the objectives of this study were to (1) demonstrate that hyperosmolar K solutions can suppress proinflammatory macrophage activation and (2) evaluate the therapeutic potential of a hyperosmolar K solution relative to a clinically utilized drug-based (methylprednisolone acetate [MPA]-a corticosteroid) or cell-based (human mesenchymal stem cell [hMSC]) IA injectable. A 3D in vitro model with poly(ethylene glycol) diacrylate hydrogels encapsulated with proinflammatory interferon-gamma (IFN)-stimulated macrophages (M(IFN)s) was utilized. Long-term changes in cell phenotype in response to short-term stimulation (i.e., mimicking an IA injection) were assessed following treatment with 80 mM K gluconate, hMSCs, or MPA. Addition of 80 mM K gluconate to culture media significantly reduced iNOS and TNF protein levels in M(IFN)s. Furthermore, short-term stimulation with K gluconate elicited a significant increase in the anti/proinflammatory cytokine profile in M(IFN)s, a response that is not noticed with either clinically utilized MPA or an hMSC injectable. Hyperosmolar K solutions are capable of attenuating proinflammatory macrophage activation. Moreover, when evaluated in an in vitro setting mimicking an IA injection, K performed significantly better than hMSCs or the corticosteroid MPA. Cumulatively, these results support further development and application of a K-based IA injection toward osteoarthritis research.
本研究的长期目标是开发一种用于治疗骨关节炎的钾（K）关节内（IA）注射剂。在这一背景下，本研究的目的是：（1）证明高渗 K 溶液可以抑制促炎巨噬细胞的激活；（2）评估高渗 K 溶液相对于临床上使用的药物（醋酸甲泼尼龙[MPA]-一种皮质类固醇）或细胞（人间充质干细胞[hMSC]）IA 注射剂的治疗潜力。利用聚乙二醇二丙烯酸酯水凝胶包裹促炎干扰素-γ（IFN）刺激的巨噬细胞（M（IFN）s）的 3D 体外模型，评估细胞表型在短期刺激（即模拟 IA 注射）后的长期变化，然后用 80mM K 葡萄糖酸、hMSC 或 MPA 进行处理。向培养基中添加 80mM K 葡萄糖酸可显著降低 M（IFN）s 中的 iNOS 和 TNF 蛋白水平。此外，K 葡萄糖酸的短期刺激可使 M（IFN）s 中的抗/促炎细胞因子谱显著增加，而这一反应在临床上使用的 MPA 或 hMSC 注射剂中并未观察到。高渗 K 溶液能够减弱促炎巨噬细胞的激活。此外，当在模拟 IA 注射的体外环境中进行评估时，K 的表现明显优于 hMSC 或皮质类固醇 MPA。综上所述，这些结果支持进一步开发和应用 K 基 IA 注射剂进行骨关节炎研究。
