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本文引用的文献

1
Effective Technical Protocol for Producing a Mono-Iodoacetate-Induced Temporomandibular Joint Osteoarthritis in a Rat Model.一种用于在大鼠模型中诱导单碘乙酸颞下颌关节骨关节炎的有效技术方案。
Tissue Eng Part C Methods. 2023 Sep;29(9):438-445. doi: 10.1089/ten.TEC.2023.0066. Epub 2023 Jul 26.
2
Temporomandibular Joint Osteoarthritis: Pathogenic Mechanisms Involving the Cartilage and Subchondral Bone, and Potential Therapeutic Strategies for Joint Regeneration.颞下颌关节骨关节炎:涉及软骨和软骨下骨的发病机制,以及关节再生的潜在治疗策略。
Int J Mol Sci. 2022 Dec 22;24(1):171. doi: 10.3390/ijms24010171.
3
Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media.通过三维培养和在化学成分明确的培养基中进行预处理来增强脐带间充质干细胞衍生的细胞外囊泡的分泌和生物活性。
Nano Converg. 2022 Dec 19;9(1):57. doi: 10.1186/s40580-022-00349-z.
4
Molecular signaling in temporomandibular joint osteoarthritis.颞下颌关节骨关节炎中的分子信号传导
J Orthop Translat. 2021 Sep 10;32:21-27. doi: 10.1016/j.jot.2021.07.001. eCollection 2022 Jan.
5
Effects of indoleamine 2, 3-dioxygenase (IDO) silencing on immunomodulatory function and cancer-promoting characteristic of adipose-derived mesenchymal stem cells (ASCs).吲哚胺 2,3-双加氧酶(IDO)沉默对脂肪间充质干细胞(ASCs)免疫调节功能和促癌特性的影响。
Cell Biol Int. 2021 Dec;45(12):2544-2556. doi: 10.1002/cbin.11698. Epub 2021 Sep 27.
6
Mesenchymal Stem Cells: Current Concepts in the Management of Inflammation in Osteoarthritis.间充质干细胞:骨关节炎炎症管理的当前概念
Biomedicines. 2021 Jul 7;9(7):785. doi: 10.3390/biomedicines9070785.
7
Pathological mechanism of chondrocytes and the surrounding environment during osteoarthritis of temporomandibular joint.颞下颌关节骨关节炎中软骨细胞及周围环境的病理机制。
J Cell Mol Med. 2021 Jun;25(11):4902-4911. doi: 10.1111/jcmm.16514. Epub 2021 May 5.
8
An Update on Mesenchymal Stem Cell-Centered Therapies in Temporomandibular Joint Osteoarthritis.颞下颌关节骨关节炎中以间充质干细胞为中心的治疗方法的最新进展
Stem Cells Int. 2021 Apr 1;2021:6619527. doi: 10.1155/2021/6619527. eCollection 2021.
9
The efficacy of mesenchymal stem cells in regenerating structures associated with the temporomandibular joint: A systematic review.间充质干细胞在颞下颌关节相关结构再生中的疗效:系统评价。
Arch Oral Biol. 2021 May;125:105104. doi: 10.1016/j.archoralbio.2021.105104. Epub 2021 Mar 6.
10
Molecular mechanisms of mechanical load-induced osteoarthritis.机械负荷诱导性骨关节炎的分子机制。
Int Orthop. 2021 May;45(5):1125-1136. doi: 10.1007/s00264-021-04938-1. Epub 2021 Jan 18.

γ干扰素预处理的脐带间充质干细胞对颞下颌关节骨关节炎的疗效

Efficacy of IFN-γ-Primed Umbilical Cord-Derived Mesenchymal Stem Cells on Temporomandibular Joint Osteoarthritis.

作者信息

Kim Hyunjeong, Kim Yerin, Yun So-Yeon, Lee Bu-Kyu

机构信息

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.

出版信息

Tissue Eng Regen Med. 2024 Apr;21(3):473-486. doi: 10.1007/s13770-023-00620-2. Epub 2024 Jan 8.

DOI:10.1007/s13770-023-00620-2
PMID:38190096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10987468/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。