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: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:Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.
| S-EPMC4791426 | biostudies-literature
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: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-1β 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.
2022-07-13 | GSE162691 | GEO
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
Project description:The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group. More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.
2022-01-27 | PXD023708 | Pride