The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Research Center, The Fourth Hospital of Hebei Medical University and The Tumor Hospital of Hebei Province, Shijiazhuang, China.
Clin Exp Rheumatol. 2020 Jul-Aug;38(4):670-679. Epub 2019 Oct 30.
Although articular cartilage contributes to smooth joint motion, once damaged this functionality cannot be recovered. Activation of the IL-6/STAT3 signalling pathway contributes to chondrogenic differentiation of mesenchymal stem cells (MSCs), indicating a role for soluble IL-6R (sIL-6R) during chondrogenesis in vitro. The aim of this study is to develop a novel therapeutic tool for regenerative medicine of articular cartilage.
Human bone marrow-derived MSCs were pre-treated with sIL-6R to direct their differentiation into chondrocytes, then seeded on a poly-lactic-co-glycolic acid (PLGA) sheet to enhance the localised residence of MSCs. The material was implanted into knee joint spaces of antigen-induced arthritis (AIA) rats, an animal model of rheumatoid arthritis (RA). After 8 weeks, the effects of the implantation on articular cartilage repair were assessed by x-ray image and staining with safranin O (S-O), aggrecan and human leukocyte antigen (HLA).
Swelling of knees in AIA rats, but not sham-treated rats, was observed. AIA rats implanted with PLGA and sIL-6R-treated MSCs showed similar knee joint imaging to sham rats using x-ray; however, those with PLGA alone, or with PLGA with MSCs, did not. Rats implanted with PLGA and sIL-6R-treated MSCs, but not PLGA alone or PLGA with MSCs, showed positive imaging by S-O staining as well as human aggrecan. HLA was not detected in the knees of any of the rats.
PLGA and sIL-6R-treated MSCs help to repair articular cartilage with high efficacy. Thus, the application of this promising strategy to regenerative medicine for articular cartilage in patients with RA is anticipated.
尽管关节软骨有助于关节运动的平滑，但一旦受损，这种功能就无法恢复。IL-6/STAT3 信号通路的激活有助于间充质干细胞（MSCs）的软骨分化，表明可溶性 IL-6R（sIL-6R）在体外软骨发生过程中发挥作用。本研究旨在开发一种用于关节软骨再生医学的新型治疗工具。
用人骨髓来源的 MSCs 预先用 sIL-6R 处理，使其向软骨细胞分化，然后接种在聚乳酸-共-羟基乙酸（PLGA）片上，以增强 MSCs 的局部居留。将该材料植入抗原诱导性关节炎（AIA）大鼠的膝关节间隙中，这是一种类风湿关节炎（RA）的动物模型。8 周后，通过 X 射线图像和番红 O（S-O）、聚集蛋白聚糖和人类白细胞抗原（HLA）染色评估植入物对关节软骨修复的影响。
AIA 大鼠的膝关节肿胀，但假手术治疗的大鼠没有观察到。用 X 射线对 AIA 大鼠进行成像，发现植入 PLGA 和 sIL-6R 处理的 MSCs 的大鼠与假手术大鼠相似；然而，仅植入 PLGA 或仅植入 PLGA 和 MSCs 的大鼠则没有。用 PLGA 和 sIL-6R 处理的 MSCs 植入的大鼠，而不是单独用 PLGA 或单独用 PLGA 和 MSCs 植入的大鼠，S-O 染色呈阳性，也检测到人类聚集蛋白聚糖。在任何大鼠的膝关节中均未检测到 HLA。
PLGA 和 sIL-6R 处理的 MSCs 有助于高效修复关节软骨。因此，预计将这一有前途的策略应用于 RA 患者的关节软骨再生医学。
