Human Mesenchymal Stem Cell-derived Knee Joint-on-a-Chip for Disease Modeling and Drug Testing

Diseases of the knee joint such as osteoarthritis affect all joint elements. A human cell-derived ex vivo model capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies/pathogenesis of joint diseases and testing potential therapeutics. Herein we generated a human mesenchymal stem cell-derived microphysiological joint-on-a-chip system (microJoint), in which engineered osteochondral, synovial, and adipose tissues were integrated into a microfluidics-enabled bioreactor. This novel design facilitated different tissues communicating while still maintaining their respective phenotypes. The microJoint exhibited physiologically relevant changes when exposed to interleukin-1ß mediated inflammation, which were similar to observations in joint diseases in humans. The potential of the microJoint in predicting in vivo efficacy of drug treatment was confirmed by testing the “therapeutic effect” of the nonsteroidal anti-inflammatory drug, naproxen, as well as four other potential disease-modifying osteoarthritis drugs. The data demonstrate that the microJoint recapitulates complex tissue interactions, thus providing a robust model for the study of joint pathology and the development of novel therapeutic interventions. Overall design: mRNA profiles of 3 types of microtissues engineered from human mesenchymal stem cells and cultured in a microfluidic device that mimics healthy and inflamed human knee joint MicroTissues used in this study: AD: engineered adipose tissue FT: engineered fibrous tissue OC-O: osseous (bone) component of the engineered osteochondral tissue OC-C: chondral (cartilage) component of the engineered osteochondral tissue