Kim Hyunjeong, Kim Yerin, Yun So-Yeon, Lee Bu-Kyu
Biomedical Engineering Research Center, Asan Medical Center, Asan Institute for Life Sciences, Seoul, Korea.
Asan Medical Center, AMIST, College of Medicine, University of Ulsan, Seoul, Korea.
Tissue Eng Regen Med. 2024 Apr;21(3):473-486. doi: 10.1007/s13770-023-00620-2. Epub 2024 Jan 8.
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA.
We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model.
IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration.
These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.
颞下颌关节骨关节炎(TMJOA)是一种影响软骨和软骨下骨的退行性疾病,可导致颞下颌关节疼痛和功能障碍。TMJOA的复杂性需要有效的替代治疗方法,而间充质干细胞(MSCs)在再生治疗中显示出了前景。本研究的目的有两个:第一,确定用于TMJOA治疗的最佳经γ干扰素(IFN-γ)预处理的MSC细胞系;第二,在TMJOA大鼠模型中全面评估源自人脐带基质的经IFN-γ预处理的间充质干细胞的治疗效果。
我们分析了MSC分泌的化合物中与OA保护相关的几个关键基因的表达变化。在此之后,我们使用Transwell系统进行共培养实验,以预测在TMJOA环境中预处理的MSCs的基因表达变化。随后,我们研究了所选的经IFN-γ预处理的源自人脐带基质的MSCs(hUCM-MSCs)在TMJOA大鼠模型中的治疗效果。
经IFN-γ预处理的MSCs表现出吲哚胺2,3-双加氧酶(IDO)、肿瘤坏死因子刺激基因6(TSG-6)和成纤维细胞生长因子2(FGF-2)表达增强。此外,与大鼠OA软骨细胞共培养可导致促炎和细胞外基质降解因子减少。在大鼠TMJOA模型中,IDO1、TSG-6和FGF2表达升高的经IFN-γ预处理的MSCs表现出强大的抗炎和治疗能力,促进了炎症环境的改善和软骨再生。
这些发现强调了在TMJOA治疗中优先减轻炎症环境的重要性,并突出了分泌这三种因子的经IFN-γ预处理的MSCs作为一种有前景的综合治疗策略。