Use of cartilage derived from murine induced pluripotent stem cells for osteoarthritis drug screening.

摘要: Objective The discovery of novel disease-modifying drugs for osteoarthritis (OA) is limited by the lack adequate genetically defined cartilage tissues application in high-throughput screening systems. We addressed this need synthesizing from induced pluripotent stem cells (iPSCs) to establish and validate an vitro model OA. Methods Native or iPSC-derived mouse samples were treated with cytokine interleukin-1α (IL-1α) 3 days inflammatory environment OA. The biochemical content, mechanical properties, gene expression resulting assayed. In addition, catabolic media was assessed. To capability, we used a 96-well plate format conducted screen previously identified candidate OA drugs. Glycosaminoglycan (GAG) release into medium as primary output screening. Results Treatment native IL-1α characteristic features rapid dose-dependent manner. addition loss GAGs tissue treatment matrix metalloproteinases increased production mediators nitric oxide prostaglandin E2. validation, all therapeutic agents provided some benefit, but only NF-κB inhibitor SC514 effectively reduced response IL-1α. Conclusion This work demonstrates utility iPSCs studying pathology provides platform identifying novel, patient-specific that prevent degradation modify course development.