Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA398528 | ENA |
REPOSITORIES: ENA
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Project description:Developmental studies and 3D in vitro model systems show the production and engagement of extracellular matrix (ECM) often precedes stem cell differentiation. Yet unclear is how the ECM triggers signaling events in sequence to accommodate multistep processes characteristic of differentiation. Here we employ transcriptome profiling and advanced imaging to delineate the specificity of ECM engagement to particular differentiation pathways and to determine whether specificity in this context is a function of long term ECM remodeling. To this end, human mesenchymal stem cells (hMSCs) were cultured in 3D bioprinted matrices created from ECM proteins and associated controls. We found exogenous ECM provided in 3D microenvironments at early time points impacts on the composition of microenvironments at later time points and that each evolving 3D microenvironment is uniquely poised to promote stem cell differentiation. Moreover, 2D cultures undergo minimal ECM remodeling and are ill-equipped to stimulate pathways associated with development.
2018-01-01 | GSE102737 | GEO
Project description:Bioprinting is an emerging additive manufacturing approach to the fabrication of patient-specific, implantable three-dimensional (3D) constructs for regenerative medicine. However, developing cell-compatible bioinks with high printability, structural stability, biodegradability, and bioactive characteristics is still a primary challenge for translating 3D bioprinting technology to preclinical and clinal models. To overcome this challenge, we develop a nanoengineered ionic covalent entanglement (NICE) bioink formulation for 3D bone bioprinting. The NICE bioinks allow precise control over printability, mechanical properties, and degradation characteristics, enabling custom 3D fabrication of mechanically resilient, cellularized structures. We demonstrate cell- induced remodeling of 3D bioprinted scaffolds over 60 days, demonstrating deposition of nascent extracellular matrix proteins. Interestingly, the bioprinted constructs induce endochondral differentiation of encapsulated human mesenchymal stem cells (hMSCs) in absence of osteoinducing agents such as dexamethasone or bone morphogenic protein-2 (BMP-2). Using next-generation transcriptome sequencing (RNA-seq) technology, we establish the role of nanosilicates, a bioactive component of NICE bioink, to stimulate endochondral differentiation at the transcriptome level. Overall, the osteoinductive bioink has the ability to induce formation of osteo-related mineralized extracellular matrix by encapsulatedhMSCsingrowthfactor-freeconditions.Furthermore,wedemonstratedtheabilityofNICEbioinktofabricatepatient-specific, implantable 3D scaffolds for repair of craniomaxillofacial bone defects. We envision transformation of this NICE bioink technology toward a realistic clinical process for 3D bioprinting patient-specific bone tissue for regenerative medicine.
2020-03-04 | GSE146309 | GEO
Project description:Pterygium is an ocular surface disorder with high prevalence that can lead to vision impairment. As a pathological outgrowth of conjunctiva, pterygium involves neovascularization and chronic inflammation, but its pathogenesis remains largely unknown. Over the last decade, various types of disease models have been built to study pterygium. Here, we developed a 3D multicellular in vitro pterygium model using the digital light processing (DLP)-based 3D bioprinting of human conjunctival stem cells (hCjSCs). A novel feeder-free culture system was adopted and efficiently expanded the primary hCjSCs with homogeneity, stemness and differentiation potency. The DLP-based 3D bioprinting was able to fabricate hydrogel scaffolds that support the viability and biological integrity of the encapsulated hCjSCs. The bioprinted 3D pterygium model was fabricated with hCjSCs, immune cells and vascular cells to recapitulate the disease microenvironment. Transcriptomic analysis using RNA sequencing (RNA-seq) identified a distinct profile correlated to inflammation response, angiogenesis, and epithelial mesenchymal transition in the bioprinted 3D pterygium model. In addition, the pterygium signatures and disease relevance of the bioprinted model were validated with the public RNA-seq data from patient-derived pterygium tissues. By integrating the stem cell technology and 3D bioprinting, this is the first reported 3D in vitro disease model for pterygium that can be utilized by future studies towards the personalized medicine and the drug screening.
2022-06-01 | GSE180343 | GEO
Project description:Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells (NPCs) in a hyaluronic acid (HA)-rich hydrogel, with or without macrophages. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-dependent functional dependencies, as well as immunologic interactions in a species-matched neural environment.
2020-11-09 | GSE147147 | GEO
Project description:Comprehensive proteomic characterization of stem cell-derived extracellular matrices
| PRJNA371782 | ENA
Project description:Therapeutic benefits of mesenchymal stem/stromal cells (MSCs) are now widely believed to come from their paracrine signalling, i.e. secreted factors such as cytokines, chemokines, and extracellular vesicles (EVs). Cell-free therapy using EVs is an active and emerging field in regenerative medicine. The cellular environment of MSCs is of critical importance when directing paracrine activity. Typical 2D cultivation of stem cells on tissue culture plastic is far removed from the physiological environment of MSCs. The application of 3D cell culture allows MSCs to adapt to their cellular niche environment which, in turn, influences their paracrine signalling activity. In this study we evaluated the impact of 3D MSCs culture on EVs secretion and cargo proteome composition and functional assessment. The outcome highlights critical differences between MSC-EVs obtained from different culture microenvironments, which should be considered when scaling up MSC culture for clinical manufacturing.
2021-11-17 | PXD029766 | Pride
Project description:Cell invasion and metastasis is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through differing and complex 3D extracellular environments. In this study we set out to identify the parameters required for invasive cell migration in 3D environments. Cells interact with the extracellular matrix via transmembrane-spanning integrin adhesion complexes. We establish a technique to determine the composition of cell-matrix adhesion complexes in invasive breast cancer cells in 3D matrices and on 2D surfaces and identify an interaction complex that is enriched in 3D adhesion sites and required for invasive migration.
2024-02-07 | PXD043063 | Pride
Project description:We have established an affordable, flexible and highly reproducible 3D bioprinted CRC model. Histological assessment of Caco-2 cells in 3D bioprints revealed the formation of glandular-like structures which show greater pathomorphological resemblance to tumours than monolayer cultures do. RNA expression profiles in 3D bioprinted cells were marked by upregulation of genes involved in cell adhesion, hypoxia, EGFR/KRAS signaling and downregulation of cell cycle programmes. Testing this 3D experimental platform with three of the most commonly used chemotherapeutics in CRC (5-fluoruracil, oxaliplatin and irinotecan), revealed overall increased resistance compared to 2D cell cultures. Lastly, we demonstrate that our workflow can be successfully extended to primary CRC samples. Thereby, we describe a novel accessible platform for disease modelling and drug testing, which may present an innovative approach in personalised therapeutic screening.
2021-11-05 | GSE181722 | GEO
Project description:The therapeutic regimens of adjuvant and neoadjuvant chemotherapy for colorectal cancer (CRC) remain largely relied on clinical experience, and thus preclinical models are needed to guide individualized medicine. The investigators are going to establish 3D bioprinted CRC models and organoids from surgically resected tumor tissues of CRC patients with or without liver metastases. In vitro 3D models and organoids will be treated with the same chemotherapy drugs with the corresponding patients from whom the models are derived. The sensitivity of chemotherapy drugs will be tested in these two types of in vitro models, and the actual response to chemotherapy in patients will be evaluated. The predictive ability of 3D models for chemotherapy sensitivity in CRC patients will be compared with that of the organoids. This observational study will validate the potential value of 3D bioprinted tumor models in predicting the response to chemotherapy in CRC.
| 2367475 | ecrin-mdr-crc
Project description:To investigate the contribution of fibroblast-derived extracellular matrices (ECMs) to the resistance to targeted therapies in BRAF-mutated melanoma cells, we generated native-like 3D ECMs from human primary fibroblasts obtained from healthy individuals or melanoma patients. Cell-derived matrices from human dermal fibroblasts (HDF), skin melanoma associated fibroblasts (MAF) and two different lymph node fibroblast reticular cells (FRC) were denuded of cells and their composition was analyzed by mass spectrometry.
2021-11-12 | PXD026645 | Pride