Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The impact of extracellular matrix on the precision medicine utility of pancreatic cancer patient-derived organoids

ABSTRACT: Organoids are cultivated in extracellular matrix from different basement membrane extracts (BMEs) that are most commonly acquired commercially. However, the impact of different sources and lots of BMEs on organoid drug response is unknown. Here, we tested the impact of BME source and lot on proliferation, chemotherapy and targeted therapy drug response, and global gene expression in mouse and human pancreatic ductal adenocarcinoma organoids. Both mouse and human organoids displayed increased proliferation in Matrigel (Corning) compared to Cultrex (RnD) and UltiMatrix (RnD). However, we observed no substantial impact on drug response when organoids were cultured in Matrigel, Cultrex, or UltiMatrix. We also did not observe major shifts in gene expression across the different BME sources.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE232170 | GEO | 2023/05/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expansion of human colonic organoids from tissue biopsies in a fully defined hydrogel matrix

Project description:Intestinal organoids have widespread applications across a variety of fields, but the dependency on basement membrane extract (BME) has hampered the transition towards clinical utilization. To overcome the limitations of BMEs, we identified an easy-to-use and fully defined extracellular matrix for the culture of human colon organoids established directly from tissue biopsies. Human colonic organoids were established from crypt-derived single cells (from six different patient samples) and cultured in QGel® CN99 or the BME benchmark Matrigel® for six culture passages (median 58 days), after which RNA was harvested for further analysis. The CN99 matrix effectively enabled organoid formation and growth, as well as efficient cell expansion, completely by-passing the use of BME. We expect this fully defined matrix to improve the reproducibility of organoid studies and to advance the translational use of the organoid technology.

2020-09-12 | GSE147133 | GEO

Suspended hydrogel culture as a method to scale up intestinal organoids

Project description:Primary tissue-derived epithelial organoids are a physiologically relevant in vitro intestinal model that have been implemented for both basic research and drug development applications. The existing method of culturing intestinal organoids in surface-attached native extracellular matrix (ECM) hydrogel domes is not readily amenable to large-scale culture and contributes to culture heterogeneity. We have developed a method of culturing intestinal organoids within suspended basement membrane extract (BME) hydrogels of various geometries, which streamlines the protocol, increases the scalability, enables kinetic sampling, and improves culture uniformity without specialized equipment or additional expertise. We demonstrate the compatibility of this method with multiple culture formats, and provide examples of suspended BME hydrogel organoids in downstream applications: implementation in a medium-throughput drug screen and generation of Transwell monolayers for barrier evaluation. The suspended BME hydrogel culture method will allow intestinal organoids, and potentially other organoid types, to be used more widely and at higher throughputs than previously possible.

2023-09-11 | GSE226539 | GEO

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoid

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to22 batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-01-31 | PXD023705 | Pride

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoids

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-02-10 | PXD023694 | Pride

Single-cell RNA-sequencing of breast cancer cells growing in invasion permissive and non-permissive 3D matrices

Project description:Murine breast cancer organoids (MMTV-PyMT) were embeded in basement membrane extract (BME, invasion non-permissive) or collagen I (invasion-permissive). Organoids were harvested after 5days for single-cell RNA-sequencing (SORT-seq).

2022-12-13 | GSE197821 | GEO

Prospective derivation of a 'Living Organoid Biobank' of colorectal cancer patients

Project description:In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design. We generated organoids from healthy tissue and coloncarcinoma tissue. The organoids were trypsinized, plated in matrigel and overlaid with medium. After three days, RNA was isolated using Qiagen RNAeasy. Medium conditions are the same for all organoids, irrespective of their origin.

2015-05-07 | E-GEOD-64392 | biostudies-arrayexpress

RNA-seq of wildtype mouse small intestinal organoids grown in Matrigel or in/on collagen.

Project description:We aimed to analyse the effect of different extra-cellular matrices on the growth of small intestinal organoids. Small intestinal crypts of wildtype mice were harvested and grown under standard Matrigel organoid conditions. After establishment of organoids (passaged 1-2), organoids were grown in Matrigel, on collagen or in a drop of collagen. Growth in a droplet of collagen requires addition of Wnt3a, therefore all samples are either provided with standard culture conditions (ENR) or with ENR+50%Wnt3a-CM (WENR). Samples were grown in specified matrix for at least 1-2 passages before RNA was purified.

2021-04-01 | E-MTAB-10082 | biostudies-arrayexpress

Human and bovine endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues.

Project description:Organoid technology has provided unique insights into human organ development, function, and diseases. Patient derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding pathological changes associated with disease progression. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined cocktail of extracellular matrix proteins and growth factors extracted from the Engelbreth Holm Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and diseases states of the same tissue. Therefore, we envisioned that extracellular matrix derived from a native healthy tissue would be sufficient to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than the organoids cultured in Matrigel. Proteomic and Raman spectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and the shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high throughput cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.

2022-03-14 | MSV000089054 | MassIVE

Examination of the role of BMP signaling in patterning of human pluripotent stem cell derived mid/hindgut spheroids and maintenance of this patterning in organoids transplanted under mouse kidney capsules.

Project description:The goal of this study was to test the hypothesis that BMP signaling regulates patterning of human CDX2+ gut tube cultures (Spence et al 2011, Watson et al. 2014). The study is comprised of 2 separate experiments. The first experiment was to determine the immediate impact of BMP signaling on CDX2+ gut tube cultures. To do so we tested spheroids, spheroids after plating in Matrigel and exposed to 3 days of Noggin (100ng/mL), spheroids after plating in Matrigel and exposed to 3 days of EGF alone (100ng/mL, Control), and spheroids after plating in Matrigel and exposed to 3 days of BMP2 (100ng/mL). RNA was collected from spheroids and spheroids after 3 days of patterning. The second experiment examined if patterning was maintained after this initial 3 days of patterning and an addition 8-10 weeks following transplantation in vivo. To do this we grew all Matrigel plated spheroids for an additional 25 days in media containing EGF alone (Control media). We then transplanted these organoids under the mouse kidney capsule and allowed them to mature for 8-10 weeks. We then collected RNA from the transplanted organoids.

2017-04-20 | E-MTAB-5658 | biostudies-arrayexpress

Effects of substrates on gene expression of human endometrial organoids

Project description:To investigate the effects of different substrates on human endometrial organoids , we compared the transcriptomes of EMO cultured within Matrigel and collagen-based gels.

2023-11-11 | GSE237245 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data