Open AccessHuman Mesenchymal Stem Cell‐Derived Miniature Joint System for Disease Modeling and Drug Testing
Author(s) -
Li Zhong,
Lin Zixuan,
Liu Silvia,
Yagi Haruyo,
Zhang Xiurui,
Yocum Lauren,
RomeroLopez 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
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202105909
Subject(s) - mesenchymal stem cell , osteoarthritis , organ on a chip , in vivo , medicine , drug , adipose tissue , inflammation , synovial fluid , drug delivery , biomedical engineering , pathology , bioinformatics , biology , immunology , pharmacology , microbiology and biotechnology , nanotechnology , materials science , microfluidics , alternative medicine
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.