@article{1531977f5e7f47ef9c385ce2702b4c4d,
title = "Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing",
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-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.",
keywords = "arthritis, human mesenchymal stem cells, inflammation in joint, joint diseases, microphysiological system",
author = "Zhong Li and Zixuan Lin and Silvia Liu and Haruyo Yagi and Xiurui Zhang and Lauren Yocum and Monica Romero-Lopez and Claire Rhee and Makarcyzk, {Meagan J.} and Ilhan Yu and Li, {Eileen N.} and Fritch, {Madalyn R.} and Qi Gao and Goh, {Kek Boon} and Benjamen O'Donnell and Tingjun Hao and Alexander, {Peter G.} and Bhushan Mahadik and Fisher, {John P.} and Goodman, {Stuart B.} and Bunnell, {Bruce A.} and Tuan, {Rocky S.} and Hang Lin",
note = "Funding Information: This research was primarily supported by funding from the National Institutes of Health (Nos. UG3/UH3TR002136 and UG3/UH3TR003090), the NIBIB Center for Engineering Complex Tissues (P41EB023833), and in part by the University of Pittsburgh Center for Research Computing through the resources provided. This study also used the UPCI Cancer Biomarkers Facility‐Luminex Core Laboratory that is supported in part by an NIH award (NCI P30CA047904). Denise Prosser is gratefully acknowledged for her assistance with the Luminex immunoassays. The authors thank Dr. Paul Manner (University of Washington) for providing the human tissue samples and Dr. Jian Tan for help in isolating hBMSCs and creating the cell pool. Funding Information: This research was primarily supported by funding from the National Institutes of Health (Nos. UG3/UH3TR002136 and UG3/UH3TR003090), the NIBIB Center for Engineering Complex Tissues (P41EB023833), and in part by the University of Pittsburgh Center for Research Computing through the resources provided. This study also used the UPCI Cancer Biomarkers Facility-Luminex Core Laboratory that is supported in part by an NIH award (NCI P30CA047904). Denise Prosser is gratefully acknowledged for her assistance with the Luminex immunoassays. The authors thank Dr. Paul Manner (University of Washington) for providing the human tissue samples and Dr. Jian Tan for help in isolating hBMSCs and creating the cell pool. Publisher Copyright: {\textcopyright} 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.",
year = "2022",
month = jul,
day = "25",
doi = "10.1002/advs.202105909",
language = "English",
volume = "9",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "21",
}