Project description:To test the utility of iPSC-derived OC tissue chip in drug screening, Celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor commonly used to treat OA, was administered to the system. Celecoxib was administered at 10 µM concentration, and showed no noticeable adverse effect on the health of normal chondral tissue. Administration of Celecoxib to both OC-C and OC-B were used to simulate the typically systemic action of Celecoxib, represented by the “SY” group. In addition, we also examined the potential effect of intraarticular (IA) application of Celecoxib in treating OA, by delivery only to OC-C, namely the “IA” group. Normal OC tissues without any treatments served as the control (CL).
Project description:In this study, we aimed to develop microphysiological osteochondral (OC) tissue chips derived from human induced pluripotent stem cells (iPSCs) to model the pathologies of OA. We first induced iPSCs into mesenchymal progenitor cells (iMPCs) and optimized the chondro- and osteo-inductive conditions for iMPCs. Then iMPCs were encapsulated into photocrosslinked gelatin scaffolds and cultured within a dual-flow bioreactor, in which the top stream was chondrogenic medium and the bottom stream was osteogenic medium. After 28 days of differentiation, biphasic OC tissue and monophasic chondral (CH) tissue chips were successfully generated and phenotypes were confirmed by real time RT-PCR. The OC tissues were cut into Top and Bottom (Bot), and both parts were compared with each other. CH tissue were compared with their phenotype on Day 0. Total RNA was extracted from the samples and processed for qPCR according to the manufacturer's instructions.
Project description:IL-1β (1 ng/ml) was introduced via medium feed to the cartilage side to induce OA-like phenotype in both OC and CH tissue chip. The catabolic, inflammatory and chondrogenic gene expression were compared between these two groups to assess the effect of osseous tissue on chondral tissue under OA condition.