Osteochondral Tissue Chip Derived from iPSCs: Modeling OA pathologies and Testing Drugs
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ABSTRACT:
PROVIDER: PRJNA589299 | ENA |
REPOSITORIES: ENA
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Project description:Osteoarthritis (OA) is a chronic disease mainly characterized by degenerative changes in cartilage, but other joint elements such as bone are also affected. To date, there are no disease-modifying OA drugs (DMOADs), owing in part to a deficiency of current models in simulating OA pathologies and etiologies in humans. 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, OC tissue chips were successfully generated and phenotypes were confirmed by real time RT-PCR and histology. To create an OA model, interleukin-1β (IL-1β) was used to challenge the cartilage component for 7 days. While under control conditions, the bone tissue promoted chondrogenesis and suppressed chondrocyte terminal differentiation of the overlying chondral tissue. Under conditions modeling OA, the bone tissue accelerated the degradation of chondral tissue which is likely via the production of catabolic and inflammatory cytokines. These findings suggest active functional crosstalk between the bone and cartilage tissue components in the OC tissue chip under both normal and pathologic conditions. Finally, a selective COX-2 inhibitor commonly prescribed drug for OA, Celecoxib, was shown to downregulate the expression of catabolic and proinflammatory cytokines in the OA model, demonstrating the utility of the OC tissue chip model for drug screening. In summary, the iPSC-derived OC tissue chip developed in this study represents a high-throughput platform applicable for modeling OA and for the screening and testing of candidate DMOADs.
| S-EPMC6930794 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-11-14 | GSE140337 | GEO
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.
2019-11-14 | GSE140332 | GEO
Project description:The global expression profile duirng chondrogenic differentiation of AC-iMSCs (#7) and OA-iMSCs (#5) was compared to determine the existance of memory of disease
2023-01-30 | GSE214987 | GEO
Project description:Synovial fluid was obtained weekly from nine horses throughout a 70-day study period and subjected to small RNA sequencing. Nine skeletally mature Standardbred trotters (seven mares and two geldings, 2.5-7 years old, weighing 397-528 kg) were included in this study. OA was surgically induced in the left middle carpal joint and the right middle carpal joint underwent sham surgery. Under arthroscopic guidance, an osteochondral fragment was created in the left middle carpal joint by chiselling off a fragment on the dorsodistal surface of the radial carpal bone using an 8 mm curved osteotome. The fragment was left adherent to the joint capsule proximally, and an incongruent defect bed of approximately 15 mm in width was created in the exposed subchondral bone between the fragment and radial carpal bone by drilling with an arthroscopic burr. Debris from the procedure was left inside the joint. Sham surgery (arthroscopy alone) was performed in the right middle carpal joint. All portals were sutured using 2-0 propylene (Surgipro, Medtronic Danmark A/S, Copenhagen, Denmark). Both carpi were bandaged with sterile dressings. Bandages were changed at day 2 and removed at day 5. Sutures were removed 10 days after surgery. From 2 weeks following OA induction and onwards, horses were exercised in 2 min of trot (4.4-5.3 m/sec) , 2 min of fast trot/gallop (9 m/sec) and 2 min of trot (4.4-5.3 m/sec) 5 days a week on a treadmill. The horses were euthanized on day 71 or 72 with an overdose of pentobarbital sodium (140 mg/kg, Euthasol Vet, Dechra Veterinary Products, Uldum, Denmark). One horse, Horse 5, was euthanized according to predefined humane endpoints at day 49, as it became lame at the walk.
2023-03-01 | E-MTAB-11840 | biostudies-arrayexpress
Project description:RNA-seq during chondrocyte differentiation of iMSCs deived from iPSCs of healthy (AC-iPSCs) and OA chondrocytes (OA-iPSCs)
| PRJNA888036 | ENA
Project description:The equine carpal osteochondral fragment model
| PRJEB53619 | ENA
Project description:Transcriptional profiling of Acinetobacter baumannii ATCC17978 cells comparing treated ethanol cells with oleanolic acid treated. Based on the gene expression, we performed experiments to confirm the therapeutic effect and mechanism of OA in A. baumannii. We performed a transcriptome anaylsis of 2 samples that are OA and ethanol treatment, respectively.
2014-08-09 | E-GEOD-60239 | biostudies-arrayexpress
Project description:Genome wide gene expression was determined in paired samples of OA affected and preserved cartilage of the same joint using microarray analysis for 33 patients of the RAAK-study. Among the 1717 genes that were significantly different expressed between OA affected and preserved cartilage we found significant enrichment for genes involved in skeletal development (e.g. TNFRSF11B and FRZB). Also several inflammatory genes such as CD55, PTGES and TNFAIP6, previously identified in within-joint analyses as well as in analyses comparing preserved cartilage from OA affected joints versus healthy cartilage were among the top genes. A notable new gene was NGF, highly up-regulated in OA cartilage. To identify gene expression profiles associated with OA processes in articular cartilage and determine pathways responsive to the disease process gene expression profiles of paired preserved and OA affected cartilage samples of the same joint were determined.
2014-07-28 | E-GEOD-57218 | biostudies-arrayexpress
Project description:Cellvibrio sp. OA-2007 genome sequencing project
| PRJDB3489 | ENA