Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing.
Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing.
复制标题
人类间充质干细胞衍生的微型关节系统用于疾病建模和药物测试。
DOI：
10.1002/advs.202105909
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发表时间：
2022-07
期刊：
影响因子：
15.1
通讯作者：
Lin, Hang
中科院分区：
文献类型：
--
作者：
Li, Zhong;Lin, Zixuan;Liu, Silvia;Yagi, Haruyo;Zhang, Xiurui;Yocum, Lauren;Romero-Lopez, Monica;Rhee, Claire;Makarcyzk, Meagan J.;Yu, Ilhan;Li, Eileen N.;Fritch, Madalyn R.;Gao, Qi;Goh, Kek Boon;O'Donnell, Benjamen;Hao, Tingjun;Alexander, Peter G.;Mahadik, Bhushan;Fisher, John P.;Goodman, Stuart B.;Bunnell, Bruce A.;Tuan, Rocky S.;Lin, Hang
关键词：
膝关节疾病，如骨关节炎（OA）影响所有关节元素。一个能够模拟关节内组织串扰的体外人细胞微生理系统是研究关节疾病的病因/发病机制和测试潜在治疗方法所需要的。在此，一个人间充质干细胞衍生的微型关节系统（miniJoint）被生成，其中工程骨软骨复合体、滑膜样纤维组织和脂肪组织被整合到一个微流体激活的生物反应器中。这种新颖的设计促进了不同组织的交流，同时仍然保持各自的表型。当暴露于白细胞介素- 1β介导的炎症时，微型关节表现出生理学上的相关变化，这与人类关节疾病的观察结果相似。通过测试非甾体抗炎药萘普生以及其他四种潜在的疾病改善OA药物的“治疗效果”，miniJoint在预测药物治疗的体内疗效方面的潜力得到了证实。数据表明，微型关节再现了复杂的组织相互作用，从而为关节病理研究和新型治疗干预的发展提供了一个强大的器官芯片模型。在微流体驱动的生物反应器中建立了一个微型滑膜关节模拟系统（miniJoint），在该系统中，人间充质干细胞衍生的骨软骨复合体、滑膜样纤维组织和脂肪组织被整合并表现出活跃的串扰。这些数据显示了miniJoint作为关节病理研究和新型治疗干预发展的新模型的潜力。
Diseases of the knee joint such as osteoarthritis (OA) affect all joint elements. An in vitro human cell‐derived microphysiological system capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies/pathogenesis of joint diseases and testing potential therapeutics. Herein, a human mesenchymal stem cell‐derived miniature joint system (miniJoint) is generated, in which engineered osteochondral complex, synovial‐like fibrous tissue, and adipose tissue are integrated into a microfluidics‐enabled bioreactor. This novel design facilitates different tissues communicating while still maintaining their respective phenotypes. The miniJoint exhibits physiologically relevant changes when exposed to interleukin‐1β mediated inflammation, which are similar to observations in joint diseases in humans. The potential of the miniJoint in predicting in vivo efficacy of drug treatment is confirmed by testing the “therapeutic effect” of the nonsteroidal anti‐inflammatory drug, naproxen, as well as four other potential disease‐modifying OA drugs. The data demonstrate that the miniJoint recapitulates complex tissue interactions, thus providing a robust organ chip model for the study of joint pathology and the development of novel therapeutic interventions. A miniature synovial joint‐mimicking system (miniJoint) is established in a microfluidics‐enabled bioreactor, in which human mesenchymal stem cell‐derived bone‐cartilage complex, synovial‐like fibrous tissue, and adipose tissue are integrated and show active crosstalk. The data demonstrate the potential of miniJoint as a new model for the study of joint pathology and the development of novel therapeutic interventions.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
27.4
作者：
Atukorala I;Kwoh CK;Guermazi A;Roemer FW;Boudreau RM;Hannon MJ;Hunter DJ
通讯作者：
Hunter DJ
影响因子：
16.1
作者：
Esch, Mandy B.;Smith, Alec S. T.;Prot, Jean-Matthieu;Oleaga, Carlota;Hickman, James J.;Shuler, Michael L.
通讯作者：
Shuler, Michael L.
影响因子：
7
作者：
de Boer, T. N.;van Spil, W. E.;Mastbergen, S. C.
通讯作者：
Mastbergen, S. C.
影响因子：
7
作者：
Fisch KM;Gamini R;Alvarez-Garcia O;Akagi R;Saito M;Muramatsu Y;Sasho T;Koziol JA;Su AI;Lotz MK
通讯作者：
Lotz MK