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Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture

ABSTRACT: Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, the clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix hydrogels derived from decellularized tissues (DT) can provide an environment capable of directing cell growth. These gels possess the biochemical signature of tissue-specific ECM, and have the potential for clinical translation. Gels from decellularized porcine small intestinal mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, liver, pancreas, and small intestine. ECM gels could be used for direct organoids derivation from human biopsies, multiple passages with transcriptomic signature comparable to gold standard culture system, and in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138611 | GEO | 2019/11/05

REPOSITORIES: GEO

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Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture

Project description:Organoids have huge therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, the clinical application is greatly limited by the lack of effective GMP-complaint systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix hydrogels derived from decellularized tissues (DT) can provide the instructive native environment necessary to direct cell growth. These gels possess the biochemical signature of tissue-specific ECM, and have the potential for clinical translation due to their natural, non-carcinogenic origin. We show that gels developed from decellularized porcine small intestinal mucosa have similar physiological range and mechanical properties to commercially available gels. ECM-derived gels enable formation and growth of endoderm-derived organoids and, moreover, supports in vivo organoid growth. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.

2019-11-05 | GSE135108 | GEO

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

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

Cholangiocyte organoid culture in hydrogels from decellularized liver tissue

Project description:Culture of human cholangiocyte organoids in hydrogels derived from healthy liver extracellular matrix (LECM) extracts prepared from decellularized human livers are evaluated in an effort to establish a platform for production of cholangiocyte organoids for clinical regenerative applications. Human intrahepatic cholangiocyte organoids (ICO) grown in hydrogels made from LECM are compared those grown in mouse tumor derived basement membrane extracts (BME). Culture was performed with amino acids labeled with stable heavy isotopes to enable separation of ECM from the hydrogels from that of the produced by the cells with mass spectrometry (MS). MS data were used to evaluate the protein production of ICO comparing the different hydrogel substrates. The study also contains evaluation of the properties of the hydrogel substrates and focuses on expansion and differentiation of the ICO.

2022-04-13 | PXD028417 | Pride

LC-MS/MS of Versatile Decellularized Human Lung Extracellular Matrix-Derived Hydrogels

Project description:Decellularized ECM (dECM) hydrogels derived from human lungs can provide valuable insight into patient-specific and lung pathophysiology. Herein, we present the approach and some initial results that highlight the unique characteristics of this dECM hydrogel platform and its benefits for a variety of potential future studies and applications.

2022-11-22 | MSV000090771 | MassIVE

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

Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels

Project description:Human salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. Here, we envisage that the use of a fully, synthetic hydrogel based on the oligo(-ethylene glycol) functionalized polymer polyisocyanopeptides (PICs) can provide an environment suitable for the generation and expansion of salivary gland organoids (SGOs) after optimization of PIC polymer properties. We demonstrate that PIC hydrogels decorated with the cell-binding peptide RGD allow SGO formation from salivary gland (SG)-derived stem cells. This self-renewal potential is preserved for only 4 passages. It was found that SGOs differentiated prematurely in PIC hydrogels affecting their self-renewal capacity. Similarly, SGOs show decreased expression of immediate early genes (IEGs) after culture in PIC hydrogels. Activation of multiple signalling pathways involved in IEG expression by β-adrenergic agonist isoproterenol, led to increased stem cell self-renewal capacity as measured by organoid forming efficiency (OFE). These results indicate that PIC hydrogels are promising 3D matrices for SGOs, with the option to be used clinically, after further optimization of the hydrogel and culture conditions.

2022-12-10 | GSE220084 | GEO

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

Project description:To determine the performance of the decellularized GI tissue ECM hydrogel, we analyzed differences in mRNA expression levels in native gastric tissues, gastric organoids cultured in Matrigel and those cultured in decellularized gastric ECM hydrogel. We also compared mRNA expression levels of native small intestinal tissues, small intestinal organoids grown in Matrigel and those grown in decellularized intestinal ECM hydrogel.

2022-01-30 | GSE165309 | GEO

Mapping of matrsisome production by alveolar epithelial cells cultured in decellularized human lung scaffolds

Project description:The alveolar epithelial cells are known producers of basement membrane components of the ECM, we hypothesize that they may also contribute substantially to remodeling of interstitial ECM in the alveolar compartment in chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Primary human alveolar type II epithelial cells (AECII) were isolated from human lungs without lung disease or with end stage COPD, using the surface marker HT2-280. Isolated cells were cryopreserved without prior expansion and then directly seeded into decellularized distal lung parenchyma from healthy human lungs. Cells were cultured for 13 days with addition of a profibrotic stimuli in the form of 2 ng/ml of TGF-ß1 at day 7, to a subgroup samples with cells derived from healthy lungs. AECII cells comes from 5 healthy cell donors and 3 with COPD, decellularized scaffolds were prepared from 5 different healthy lungs. The data set contains a total of 71 samples each representing a unique cell/scaffold/treatment combination at either day7 or day 13 of culture. For each sample there exists a matched proteomics sample from mass spectrometry analysis deposited to the ProteomeXchange Consortium via the PRIDE partner repository. The data indicate a substantial potential of alveolar epithelial cells to directly contribute to matrisome turnover and ECM remodeling in the lung.

2022-10-31 | GSE191279 | GEO

Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

Project description:As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by LC-QTOF-MS facing the challenge of capturing metabolic information from minimal sample amount (< 500 cells/injection) in the presence of extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on p-value and fold change cut-offs which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2'-deoxyuridine, 2'-O-methylcytidin, inosine and 1-methyladenosine and depletion of 2'-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.

2021-10-12 | MTBLS2130 | MetaboLights

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