Cancer therapy induced effects on lung organoids as suitable in vitro model
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PROVIDER: PRJNA1151650 | ENA |
REPOSITORIES: ENA
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Project description:Generation of lung organoids as model for genotoxic stress
2024-12-27 | GSE275539 | GEO
Project description:The individualized treatment of tumors has always been an urgent problem in clinical practice. Organoids-on-a-chip can reflect the heterogeneity of tumors and is a good model for in vitro anticancer drug screening. In this study, surgical specimens of patients with advanced colorectal cancer will be collected for organoid culture and organoids-on-a- chip. Use organoids-on-a-chip to screen tumor chemotherapy drugs, compare the results of patients’ actual medication regimens, and study the guiding role of organoids in the formulation of precise tumor treatment plans. The investigators will compare the response of organoids to drugs in vitro with the patient’s response to actual chemotherapy and targeted drugs and explore the feasibility and accuracy of organoids-on-a-chip based drug screening for advanced colorectal cancer. The project will establish a screening platform for chemotherapeutic drugs and targeted drugs based on colorectal cancer organoids to quickly and accurately formulate personalized treatment plans for clinical patients.
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Project description:Drug toxicity screening on retina is essential for the development of safe therapies for a large number of diseases, whilst preserving visual acuity and function. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide a suitable screening platform due to their similarity to human retina and the ease of generation in large-scale formats, offering almost unlimited excess of tissue. Two hPSC cell lines were differrentiated to retinal organoids which comprised all key retinal cell types in multiple nuclear and synaptic layers, enabling the maintenance of retinal ganglion and bipolar cells and moreover allowed the development of subtypes as revealed by the single cell RNA-Seq analysis. Ketorolac, Digoxin, Thioridazine, Sildenafil, Ethanol and Methanol were used to screen drug effects on retinal organoids. Exposure of the hPSC-derived retinal organoids to Diogxin, Thioridazine and Sildenafil exposure resulted in photoreceptor cell death, while Digoxin and Thioridazine additionally affected all other cell types, including Müller glia cells. Ethanol and Methanol caused an upregulation in retinal ganglion cell related geneexpression. All drug treatments activated astrocytes, indicated by dendrites sprouting into neuroepithelium and upregulation of astrocyte related genes. The ability to resond to light was presereved in organoids although the number of active retinal ganglion cells decreased after drug expsoure. These data indicate comparable drug effects in organoids to those reported in in vitro models and/or in humans, thus providing first robust experimental evidence of their suitability for toxicological studies.
2023-03-03 | GSE172138 | GEO
Project description:The development and progression of endometriotic lesions are poorly understood, but immune cell dysfunction and inflammation are closely associated with the pathophysiology of endometriosis. A lack of suitable 3D in vitro models permitting the study of interactions between cell types and the microenvironment is a contributing factor. To address this limitation, we developed endometriotic organoids (EO) to explore the role of epithelial-stromal interactions and model peritoneal cell invasion associated with lesion development. Using a non-adherent microwell culture system, spherical organoids were generated with endometriotic epithelial cells (12Z) combined with immortalized endometriotic stromal cells (iEc-ESC) or immortalized uterine stromal cells (iHUF). Organoids self-organized with stromal cells occupying the center and epithelial cells on the periphery of the organoid. Endometriotic organoids (EO), containing iEc-ESC, resulted in the development of stratified 12Z epithelial cells compared to those with iHUF where the 12Z cells developed as a single layered epithelium. Transcriptomic analysis found 4,522 differentially expressed genes (DEG) between EO and 12Z/iHUF organoids, and the top DEG included increased expression of interleukins and prostaglandin synthase enzymes. An overlap of the EO DEG with baboon endometriotic lesions was highly significant. Finally, to mimic invasion of endometrial tissue into the peritoneum, a model was developed using EO and extracellular matrix containing human peritoneal mesothelial cells (LP9). Invasion of EO into the extracellular matrix-LP9 layer was increased in presence of estrogen or THP1-derived proinflammatory macrophages. Taken together, our results strongly support the concept that EO are an appropriate model for dissecting mechanisms that contribute to endometriotic lesion development.
2022-06-15 | GSE202661 | GEO
Project description:Retinal organoids provide a suitable tool for toxicological drug screening – a comprehensive study validating well-known drug effects on retinal organoids
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Project description:Schwann cells (SCs) are not only decisive to produce the axon-wrapping myelin sheath thus ensuring a proper nerve conduction but also exhibit with trophic function and can direct repair mechanisms of the peripheral nervous system. Consequently, suitable and well-characterized SC in vitro models are needed to perform appropriate pre-clinical studies including the investigation of the complex biochemical adaptations occurring in the peripheral nervous system (PNS) under different (patho)physiological conditions. MSC80 cells represent a SC line derived from mouse used in laboratories as a suitable in vitro system for neuropathological studies. As a comprehensive MSC80 protein catalogue remained elusive, here we introduce the most abundant 9532 proteins identified via mass spectrometry based protein analytics and thus provide the most comprehensive SC protein catalogue published thus far. Hereby, not only proteins causative for inherited neuropathies were covered but it has also been demonstrated that apart from cytoplasmic and nuclear proteins, mitochondrial proteins and such belonging to the protein processing machinery are very well covered. Moreover, we addressed the suitability of MSC80 to examine molecular effect of a drug-treatment by analyzing the proteomic signature of Vitamin C-treated MSC80 cells. Proteomic findings along with further immunological and functional experiments support the concept of a beneficial role influence of Vitamin C on oxidative stress and identified TMX1 as an oxidative stress protective factor in SC which might represent a promising target for therapeutic intervention of PNS disorders with marked oxidative stress burden such as diabetic neuropathy.
2018-08-13 | PXD006910 | Pride
Project description:Gene expression changes of human colon orgnaoids by 60weeks of inflammatory stimulation in vitro (long-term inflammed organoids) and after 10weeks from the removal of stimulation (inflammation-removed organoids). GSEA analysis was performed about RNA1-9 (Organoids #1). For the reproducibility of the analysis, GSEA was performed in triplicate. The key molecule for long-term inflammation was extracted from RNA10-12 (Organoids #2). The comparison of gene expression of organoids derived from normal(RNA1-3) and UC mucosa(RNA13-15). For the reproducibility, the analysis was performed in triplicate.
2020-10-26 | GSE156806 | GEO
Project description:Endometriotic Organoids: A Novel In Vitro Model of Endometriotic Lesion Development
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Project description:In this study, midbrain-like organoids were yielded from hPSCs to prepare cells suitable for PD therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into mDA neurons, and an unprecedentedly high proportion express midbrain-specific factors.
2020-01-23 | GSE144062 | GEO
Project description:Mutations in the cone-rod homeobox (CRX) transcription factor lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Using induced pluripotent stem cells (iPSCs) from a patient with CRX-I138fs mutation, we established an in vitro model of CRX-LCA in retinal organoids that exhibit defective photoreceptor maturation by histology and gene profiling including diminished expression of visual opsins. Gene therapy by delivery of an additional correct CRX allele using an AAV vector partially restored photoreceptor phenotype and expression of phototransduction-related genes as revealed by single cell RNA-sequencing. Retinal organoids derived from iPSCs of a second dominant CRX-LCA patient carrying a K88N mutation revealed loss of opsin expression as a common phenotype, which could also be alleviated by AAV-mediated overexpression of CRX. Our studies provide the proof-of-concept for development of gene therapy for dominant CRX-LCA and other CRX-retinopathies.
2021-02-17 | GSE153099 | GEO