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Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer. OBJECTIVE: To study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established. DESIGN: Human endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues. Organoids were treated for 14 days with physiologic levels of estradiol and…

Rotavirus Infection and Cytopathogenesis in Human Biliary Organoids Potentially Recapitulate Biliary Atresia Development.

Biliary atresia (BA) is a neonatal liver disease characterized by progressive fibroinflammatory obliteration of both intrahepatic and extrahepatic bile ducts. The etiologies of BA remain largely unknown, but rotavirus infection has been implicated at least for a subset of patients, and this causal relation has been well demonstrated in mouse models. In this study, we aim to further consolidate this evidence in human biliary organoids. We obtained seven batches of human biliary organoids cultured from fetal liver, adult liver, and bile duct tissues. We found that these organoids are highly susc…

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, … heckpoint kinase ATR. RESULTS: MMC was more effective in eliminating peritoneal metastasis-derived organoids than oxaliplatin at clinically relevant concentrations. However, the drug concentrations required to eliminate 50 per cent of the tumour cells (IC50) were higher than the median clinical dose in two of five organoid lines for MMC, and all five lines …

In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.

Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models…

FGF2-dependent mesenchyme and laminin-111 are niche factors in salivary gland organoids.

Epithelial progenitor cells are dependent upon a complex 3D niche to promote their proliferation and differentiation during development, which can be recapitulated in organoids. The specific requirements of the niche remain unclear for many cell types, including the proacinar cells that give rise to secretory acinar epithelial cells that produce saliva. Here, using ex vivo cultures of E16 primary mouse submandibular salivary gland epithelial cell clusters, we investigated the requirement for mesenchymal cells and other factors in producing salivary organoids in culture. Native E16 salivary mes…

A novel morphometry system automatically assessing the growth and regeneration of intestinal organoids.

As compared with 2D cell line cultures, 3D intestinal organoids are better at maximally recapitulating the physiological features of stem cells in vivo. However, the complex 3D structure is an obstacle which must be objectively and automatically evaluated to assess colony growth and regeneration. Meanwhile, no internal standard currently exists for evaluating the size of heterogeneities in organoids or defining those regenerating colonies. Herein, we developed a simple morphometry system to image MTT-stained organoids. The growth curve of organoids can be automatically generated based upon ana…

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurode…

From organoids to organs: Bioengineering liver grafts from hepatic stem cells and matrix.

Due to the complex function and structure of the liver, resourceful solutions for treating end-stage liver disease are required. Currently, liver transplantation is the only curative therapeutic option. However, due to a worldwide donor shortage, researchers have been looking in other fields for alternative sources of transplantable liver tissue. Recent advances in our understanding of liver physiology, stem cell and matrix biology, have accelerated tissue engineering research. Most notable is the discovery of a culture system to grow liver-like organoids from human hepatic stem cells. The ext…

Esophageal Adenocarcinoma-Derived Extracellular Vesicle MicroRNAs Induce a Neoplastic Phenotype in Gastric Organoids.

There have been no reports describing the effects of cancer cell-derived extracellular vesicles (EVs) on three-dimensional organoids. In this study, we delineated the proneoplastic effects of esophageal adenocarcinoma (EAC)-derived EVs on gastric organoids (gastroids) and elucidated molecular mechanisms underlying these effects. EVs were identified using PKH-67 staining. Morphologic changes, Ki-67 immunochemistry, cell viability, growth rates, and expression levels of miR-25 and miR-210, as well as of their target mRNAs, were determined in gastroids co-cultured with EAC-derived extracellular v…

1 Заражение мозговых организмов человека и панкреатических стволовых клеток движет органоидно-специфическими транскриптами, связанными с болезнью Альцгеймера и аутоиммунными заболеваниями.

Вирусные инфекции, ведущие к воспалению, были связаны с несколькими распространенными заболеваниями, такими, как болезнь Альцгеймера (AD) и диабет типа 1 (T1D). Следует отметить, что, согласно сообщениям, герпес симплекс-вирус 1 (HSV-1) связан с AD. Мы пытались выявить трансформационные изменения, вызванные инфекцией HSV-1 и антивирусным наркотиком (ацикловирус, ACV) для лечения инфекции HSV-1 в отделенных клетках от человеческих церебральных органидов (dcOrgs) по сравнению с поджелудочными изотопами, полученными из стволовых клеток (sc-syslets), с тем чтобы получить потенциальное биологическо

Совпадение в аннотации оригинала
Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer's disease (AD) and type 1 diabet … i-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets …

Updated Protocols for 3D and 2D Culture and Histological Analysis of Intestinal Organoids.

The intestinal epithelium maintains continuous self-renewal and multi-differentiation capacities through the integrated regulation of multiple signaling pathways, including Wnt, bone morphogenetic protein, epidermal growth factor (EGF), and Notch signaling pathways. Based on this principle, a defined combination of EGF, Noggin, and the Wnt agonist R-spondin has been shown to support long-term expansion of mouse intestinal stem cells and the formation of organoids with indefinite self-renewal and full differentiation capacity. In human intestinal organoid cultures, the addition of small molecul…

Nanoplasmonic Aptasensing Enables Real-Time Optical Monitoring of Neurotransmitters in Living Brainstem Organoids.

Disruption of dopamine signaling is central to Parkinson's disease (PD) pathology and a primary target of symptomatic therapy. However, direct measurement of dopamine dynamics in human neural tissue with high sensitivity, temporal resolution, and compatibility with three-dimensional models remains technically challenging. Here, an organoid-on-a-chip platform that integrates a cavity-coupled nanoplasmonic aptasensor with human brainstem organoids (hBSOs) and microfluidic control is employed for label-free monitoring of the extracellular dopamine response. The plasmonic aptasensor achieves a lim…

Differential toxicity of water- and DMSO-extractable PM2.5 fractions in human alveolar organoids.

PM2.5 is a major air pollutant associated with the onset and exacerbation of various diseases. However, due to the lack of suitable experimental models, the damage caused by PM2.5 to the organism and its relationship with diseases remain poorly understood. This study aims to establish a toxicity exposure model for PM2.5 using human alveolar organoids (hALOs) and investigate the differences in alveolar damage caused by water-extractable fraction and DMSO-extractable fraction of PM2.5. The results revealed that PM2.5 induced morphological damage in hALOs in a dose- and time-dependent manner, wit…

Generation of synthetic vascular organoids via orthogonal programming of human pluripotent stem cells.

The development of functional human vasculature is essential for tissue engineering, disease modeling, and regenerative medicine. Conventional differentiation protocols of vascular lineages often exhibit lineage heterogeneity and limited control over cellular ratios. Here, we describe a protocol for generating vascular organoids (VOs) via orthogonal forward programming of hPSCs. By utilizing doxycycline-inducible activation of the transcription factors ETV2 and NKX3.1, hPSCs are rapidly directed toward endothelial and mural cell lineages, respectively. This strategy enables the assembly of VOs…

From sebocytes to skin engineering human sebaceous organoids within a reconstructed dermal matrix.

INTRODUCTION: Sebaceous gland biology depends on the integration of lipid metabolism, tissue architecture, and stromal interactions, yet most available in vitro systems fail to capture these features simultaneously. This work reports the generation of a functional three-dimensional (3D) sebaceous gland organoid embedded within a matrix and designed to reproduce the structural and functional properties of native sebaceous tissue. METHODS: Using SZ95 sebocytes, we first established baseline responses in monolayer conditions using linoleic acid (LA) stimulation and pharmacological inhibition wit

Human airway organoids for bacterial-host interaction studies: methods, insights and translational promise.

BACKGROUND: The global burden of bacterial respiratory infections, now among the leading causes of mortality worldwide, has been exacerbated by the rise of antimicrobial resistance. This has highlighted significant gaps in current management strategies, underscoring the need for deeper insights into bacterial pathogenesis. METHODS: This review assesses the utility of various experimental models for achieving human relevance and explores recent innovations in human airway organoid (HAO) technology for modelling bacterial infections. RESULTS: Human airway organoid models offer a promising solu

Tumor immune microenvironment reconstitution in patient-derived organoids enables therapy modeling for NSCLC.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Despite various therapeutic options, treatment resistance is common, underscoring the need for effective combination therapies and reliable pre-clinical models for patient-specific evaluation. Here, we describe strategies for reconstituting tumor immune microenvironment (TIME) components within patient-derived tumor organoid (PDTO) cultures. We established a tumor processing pipeline that enables concurrent expansion of tumor-infiltrating lymphocytes (TILs) and PDTO generation from the same resection. We op