Human Mesenchymal Stem Cell‐Derived Miniature Joint System for Disease Modeling and Drug Testing. Issue 21 (18th April 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Advanced science. Volume 9:Issue 21(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-18
• Subjects: arthritis -- human mesenchymal stem cells -- inflammation in joint -- joint diseases -- microphysiological system; Science -- Periodicals; 505
• DOI: 10.1002/advs.202105909
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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‐1 β 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. Abstract : 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.