• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

构建用于类风湿性关节炎研究的3D共培养滑膜组织模型。

Constructing a 3D co-culture synovial tissue model for rheumatoid arthritis research.

作者信息

Wang Xiaocheng, He Jiaxin, Zhang Qiang, He Juan, Wang Qingwen

机构信息

Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.

Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.

出版信息

Mater Today Bio. 2025 Jan 24;31:101492. doi: 10.1016/j.mtbio.2025.101492. eCollection 2025 Apr.

DOI:10.1016/j.mtbio.2025.101492
PMID:39968522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11834117/
Abstract

The development and exploration of highly effective drugs for rheumatoid arthritis remains an urgent necessity. However, current disease research models are no longer sufficient to meet the rapid development of high-throughput drug screening. In this study, bacterial cellulose simulating the structure of extracellular matrix was used as a 3D culture platform, and THP-1-derived M1 macrophages, representing the inflammatory component, human umbilical vein endothelial cells (HUVECs), simulating the vascular component, and rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), embodying the synovial pathology, were co-cultured to simulate the pathological microenvironment in RA synovial tissues, and synovial organoids were constructed. Under three-dimensional (3D) culture conditions, there was a notable upregulation of fatty acid-binding protein 4 (FABP4) in polarized macrophages, and an enhancement of pathological phenotypes in HUVECs and RA-FLSs, mediated through the PI3K/AKT signaling pathway, including cell proliferation, migration, invasion and vascularization. Compared to planar cultures and 2D co-cultures, 3D synovial organoids not only exhibit a broader range of transcriptomic features characteristic of rheumatoid arthritis but also demonstrate increased drug resistance, likely due to the more complex and physiologically relevant cell-cell and cell-matrix interactions present in 3D environments. This model offers a promising path for personalized treatment, accelerating precision medicine in rheumatology.

摘要

开发和探索治疗类风湿性关节炎的高效药物仍然是当务之急。然而，当前的疾病研究模型已不足以满足高通量药物筛选的快速发展。在本研究中，模拟细胞外基质结构的细菌纤维素被用作三维培养平台，将代表炎症成分的THP-1衍生的M1巨噬细胞、模拟血管成分的人脐静脉内皮细胞（HUVECs）以及体现滑膜病理的类风湿性关节炎成纤维细胞样滑膜细胞（RA-FLSs）共培养，以模拟类风湿性关节炎滑膜组织中的病理微环境，并构建滑膜类器官。在三维（3D）培养条件下，极化巨噬细胞中脂肪酸结合蛋白4（FABP4）显著上调，HUVECs和RA-FLSs的病理表型增强，这是通过PI3K/AKT信号通路介导的，包括细胞增殖、迁移、侵袭和血管生成。与平面培养和二维共培养相比，三维滑膜类器官不仅表现出更广泛的类风湿性关节炎特征转录组学特征，而且还表现出耐药性增加，这可能是由于三维环境中存在更复杂且与生理相关的细胞-细胞和细胞-基质相互作用。该模型为个性化治疗提供了一条有前景的途径，加速了风湿病学的精准医疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/332338861ecc/mmcfigs21.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/2db12514a7e0/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/4e76e880a241/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/bf102ff11a81/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/ec7db417968f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/b82f7c242a3c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/5b5e60d1ac61/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/8d718bc50202/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/91b745403f35/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/dc94a1490676/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/36e1b607f3c2/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/db7ef0534203/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/e8b9e089edef/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/1cd02f452a69/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/cd9a0feceb63/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/c4767c859353/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/ab8432ae3bb6/mmcfigs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/4757cf56a35e/mmcfigs7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/58b3ae85fd57/mmcfigs8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/d700f968a874/mmcfigs9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/681b48db8f9b/mmcfigs10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/920f3add0d8c/mmcfigs11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/7ab317a61fcb/mmcfigs12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/3023058f25ac/mmcfigs13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/c66a0b4c2f75/mmcfigs14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/4bcb528c83c6/mmcfigs15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/c143c3e3544f/mmcfigs16.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/522d3025f4b8/mmcfigs17.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/f0e848a5ec4c/mmcfigs18.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/64dd7f0f431a/mmcfigs19.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/8c5159409847/mmcfigs20.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/332338861ecc/mmcfigs21.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/2db12514a7e0/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/4e76e880a241/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/bf102ff11a81/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/ec7db417968f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/b82f7c242a3c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/5b5e60d1ac61/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/8d718bc50202/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/91b745403f35/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/dc94a1490676/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/36e1b607f3c2/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/db7ef0534203/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/e8b9e089edef/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/1cd02f452a69/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/cd9a0feceb63/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/c4767c859353/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/ab8432ae3bb6/mmcfigs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/4757cf56a35e/mmcfigs7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/58b3ae85fd57/mmcfigs8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/d700f968a874/mmcfigs9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/681b48db8f9b/mmcfigs10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/920f3add0d8c/mmcfigs11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/7ab317a61fcb/mmcfigs12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/3023058f25ac/mmcfigs13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/c66a0b4c2f75/mmcfigs14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/4bcb528c83c6/mmcfigs15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/c143c3e3544f/mmcfigs16.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/522d3025f4b8/mmcfigs17.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/f0e848a5ec4c/mmcfigs18.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/64dd7f0f431a/mmcfigs19.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/8c5159409847/mmcfigs20.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e15/11834117/332338861ecc/mmcfigs21.jpg

相似文献

1
Constructing a 3D co-culture synovial tissue model for rheumatoid arthritis research.构建用于类风湿性关节炎研究的3D共培养滑膜组织模型。
Mater Today Bio. 2025 Jan 24;31:101492. doi: 10.1016/j.mtbio.2025.101492. eCollection 2025 Apr.
2
A novel 3D spheroid model of rheumatoid arthritis synovial tissue incorporating fibroblasts, endothelial cells, and macrophages.一种新型的类风湿关节炎滑膜组织的 3D 球体模型，包含成纤维细胞、内皮细胞和巨噬细胞。
Front Immunol. 2023 Jul 20;14:1188835. doi: 10.3389/fimmu.2023.1188835. eCollection 2023.
3
uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis.uPAR 通过 PI3K/Akt 信号通路促进类风湿关节炎患者成纤维样滑膜细胞的肿瘤样生物学行为。
Cell Mol Immunol. 2018 Feb;15(2):171-181. doi: 10.1038/cmi.2016.60. Epub 2017 Jan 16.
4
Schisandrin treatment suppresses the proliferation, migration, invasion, and inflammatory responses of fibroblast-like synoviocytes from rheumatoid arthritis patients and attenuates synovial inflammation and joint destruction in CIA mice.五味子素治疗可抑制类风湿关节炎患者成纤维样滑膜细胞的增殖、迁移、侵袭和炎症反应，并减轻 CIA 小鼠的滑膜炎症和关节破坏。
Int Immunopharmacol. 2023 Sep;122:110502. doi: 10.1016/j.intimp.2023.110502. Epub 2023 Jun 28.
5
A Novel Phytochemical, DIM, Inhibits Proliferation, Migration, Invasion and TNF-α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway.一种新型植物化学物质 DIM 通过靶向 MAPK 和 AKT/mTOR 信号通路抑制类风湿关节炎患者滑膜成纤维细胞的增殖、迁移、侵袭和 TNF-α 诱导的炎症细胞因子产生。
Front Immunol. 2019 Jul 23;10:1620. doi: 10.3389/fimmu.2019.01620. eCollection 2019.
6
Single-Cell Multi-Dimensional data analysis reveals the role of ARL4C in driving rheumatoid arthritis progression and Macrophage polarization dynamics.单细胞多维数据分析揭示了 ARL4C 在驱动类风湿关节炎进展和巨噬细胞极化动态中的作用。
Int Immunopharmacol. 2024 Nov 15;141:112987. doi: 10.1016/j.intimp.2024.112987. Epub 2024 Aug 24.
7
Arecoline hydrobromide suppresses PI3K/AKT pathway in rheumatoid arthritis synovial fibroblasts and relieves collagen-induced arthritis in mice.氢溴酸槟榔碱可抑制类风湿关节炎滑膜成纤维细胞中的 PI3K/AKT 通路，并缓解胶原诱导的关节炎小鼠模型的症状。
Int Immunopharmacol. 2023 Nov;124(Pt B):110925. doi: 10.1016/j.intimp.2023.110925. Epub 2023 Sep 22.
8
Nitidine chloride inhibits fibroblast like synoviocytes-mediated rheumatoid synovial inflammation and joint destruction by targeting KCNH1.氯化两面针碱通过靶向 KCNH1 抑制成纤维样滑膜细胞介导的类风湿性滑膜炎症和关节破坏。
Int Immunopharmacol. 2021 Dec;101(Pt A):108273. doi: 10.1016/j.intimp.2021.108273. Epub 2021 Oct 29.
9
LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis.LncRNA PICSAR 通过海绵吸附 miRNA-4701-5p 促进类风湿关节炎成纤维样滑膜细胞的增殖、迁移和侵袭。
EBioMedicine. 2019 Dec;50:408-420. doi: 10.1016/j.ebiom.2019.11.024. Epub 2019 Nov 30.
10
Constitutive Activation of Integrin α9 Augments Self-Directed Hyperplastic and Proinflammatory Properties of Fibroblast-like Synoviocytes of Rheumatoid Arthritis.整合素α9的组成性激活增强类风湿关节炎成纤维样滑膜细胞的自我导向增生和促炎特性。
J Immunol. 2017 Nov 15;199(10):3427-3436. doi: 10.4049/jimmunol.1700941. Epub 2017 Oct 16.

引用本文的文献

1
Pharmacological Inhibition of the PI3K/AKT/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical).类风湿性关节炎滑膜细胞中PI3K/AKT/mTOR信号通路的药理学抑制作用：一项系统评价和荟萃分析（临床前研究）
Pharmaceuticals (Basel). 2025 Aug 2;18(8):1152. doi: 10.3390/ph18081152.
2
Immune Organoids: A Review of Their Applications in Cancer and Autoimmune Disease Immunotherapy.免疫类器官：其在癌症和自身免疫性疾病免疫治疗中的应用综述
Curr Issues Mol Biol. 2025 Aug 13;47(8):653. doi: 10.3390/cimb47080653.
3
Synovial organoids: From fundamental construction to groundbreaking applications in arthritic disorders.

本文引用的文献

1
A novel 3D spheroid model of rheumatoid arthritis synovial tissue incorporating fibroblasts, endothelial cells, and macrophages.一种新型的类风湿关节炎滑膜组织的 3D 球体模型，包含成纤维细胞、内皮细胞和巨噬细胞。
Front Immunol. 2023 Jul 20;14:1188835. doi: 10.3389/fimmu.2023.1188835. eCollection 2023.
2
Construction of engineered 3D islet micro-tissue using porcine decellularized ECM for the treatment of diabetes.使用猪去细胞细胞外基质构建工程化 3D 胰岛微组织用于治疗糖尿病。
Biomater Sci. 2023 Aug 8;11(16):5517-5532. doi: 10.1039/d3bm00346a.
3
A matrigel-free method for culture of pancreatic endocrine-like cells in defined protein-based hydrogels.
滑膜类器官：从基础构建到在关节炎疾病中的突破性应用
J Orthop Translat. 2025 Jul 16;54:26-36. doi: 10.1016/j.jot.2025.07.004. eCollection 2025 Sep.
4
Harnessing organoid technology to model autoimmune pathways in rheumatological and inflammatory disorders.利用类器官技术模拟风湿性和炎症性疾病中的自身免疫途径。
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 15. doi: 10.1007/s00210-025-04387-2.
一种在特定蛋白基水凝胶中培养胰腺内分泌样细胞的无基质胶方法。
Front Bioeng Biotechnol. 2023 Mar 9;11:1144209. doi: 10.3389/fbioe.2023.1144209. eCollection 2023.
4
Signaling pathways in rheumatoid arthritis: implications for targeted therapy.类风湿关节炎中的信号通路：靶向治疗的意义。
Signal Transduct Target Ther. 2023 Feb 17;8(1):68. doi: 10.1038/s41392-023-01331-9.
5
Rheumatoid Arthritis - Common Origins, Divergent Mechanisms.类风湿关节炎——共同起源，不同机制。
N Engl J Med. 2023 Feb 9;388(6):529-542. doi: 10.1056/NEJMra2103726.
6
Highly efficient fabrication of functional hepatocyte spheroids by a magnetic system for the rescue of acute liver failure.高效制备功能性肝细胞球体的磁系统，用于急性肝衰竭的救治。
Biomaterials. 2023 Mar;294:122014. doi: 10.1016/j.biomaterials.2023.122014. Epub 2023 Jan 20.
7
High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month.高效构建类骨痂器官样体以实现一个月内的快速骨再生。
Biomaterials. 2022 Sep;288:121741. doi: 10.1016/j.biomaterials.2022.121741. Epub 2022 Aug 19.
8
Synovial joint-on-a-chip for modeling arthritis: progress, pitfalls, and potential.芯片上的滑膜关节用于关节炎建模：进展、陷阱和潜力。
Trends Biotechnol. 2023 Apr;41(4):511-527. doi: 10.1016/j.tibtech.2022.07.011. Epub 2022 Aug 19.
9
FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis.M1极化巨噬细胞分泌的脂肪酸结合蛋白4（FABP4）促进滑膜炎和血管生成，从而加重类风湿性关节炎。
Bone Res. 2022 Jun 22;10(1):45. doi: 10.1038/s41413-022-00211-2.
10
Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission.滑膜组织巨噬细胞在关节稳态、类风湿关节炎和疾病缓解中的作用。
Nat Rev Rheumatol. 2022 Jul;18(7):384-397. doi: 10.1038/s41584-022-00790-8. Epub 2022 Jun 7.