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Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons and the accumulation of Lewy-body protein aggregates containing misfolded α-synuclein (α-syn) in a phosphorylated form. The lack of effective models for drug screens has hindered drug development studies for PD. However, the recent development of in vitro brain-like organoids provides a new opportunity for evaluating therapeutic agents to slow the progression of this chronic disease. METHODS: In this study, we used a 3D brain-like organoid model to investigate the potential …

Natural Hydrogels Support Kidney Organoid Generation and Promote In Vitro Angiogenesis.

To date, strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. … noid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endoth …

A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening.

Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrom … val. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencin …

A Novel Use of Embryonic Gut Organoid Culture to Investigate Duodenal Atresia.

BACKGROUND: The cause of duodenal atresia (DA) is not known. Tandler's "solid cord" hypothesis conflicts with current biological evidence. In humans, a genetic aetiology is supported by the association with Trisomy 21. Interruption of Fgf10 is the strongest genetic link to DA in mice, demonstrating an increased incidence and severity as embryos mature. This project aimed to develop an organoid model to facilitate ex vivo DA research on the FGF10/FGFR2b signalling pathway. We hypothesised that DA morphology represents an evolving spectrum of disease and that Fgf10 knockout organoids would vary …

Методологии изучения мозговых органоидов для изучения механизмов заболевания в прогрессивном множественном склерозе.

Множественный склероз (MS) — изнуряющее аутоиммунное расстройство, направленное против центральной нервной системы (CNS), отмечен непрерывным обезвоживанием и воспалением. В клинической форме она представляет в трех различных формах: повторные выбросы MS (RRMS), первичные прогрессивные MS (PPMS) и вторичные прогрессивные MS (SPMS). Несмотря на то, что лечение с целью изменения болезней (ДМР) оказывает определенное содействие людям, страдающим СВЗ, варианты лечения прогрессивных СЗМ (ПМС) по-прежнему являются крайне неадекватными. Этот пробел свидетельствует о настоятельной необходимости примен

Совпадение в аннотации оригинала
Multiple sclerosis (MS), a debilitating autoimmune disorder targeting the central nervous system (CNS), is marked by relentless demyelinatio … l the intricate pathology of pMS. Human induced pluripotent stem cell (iPSC) technologies and brain organoids are emerging as promising tools for disease modeling in both 2D and 3D in vitro environments. These innovative approaches enable the study of disease mechanisms that closely mimic human pathophysiology and offer new platforms for screening therapeut …

Establishment of Epithelial Inflammatory Injury Model Using Intestinal Organoid Cultures.

Intestinal epithelial dysfunction is critical in the development of inflammatory bowel disease (IBD). However, most cellular experiments related to epithelial barrier studies in IBD have been based on tumor cell line that lack a variety of intestinal epithelial cell types. Thus, intestinal organoids can present the three-dimensional structure and better simulate the physiological structure and function of the intestinal epithelium in vitro. Here, the crypts were isolated from the small intestine of mice; with the participation of major cytokines (EGF, Noggin, and R-Spondin 1 included), the int…

3D hepatic organoid production from human pluripotent stem cells.

Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we descri…

An integrated organoid omics map extends modeling potential of kidney disease.

Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed …

Human organoid systems in modeling reproductive tissue development, function, and disease.

Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited … odeling human reproductive organ development have been made. These cultures, broadly referred to as organoids, enable research aimed at understanding cellular hierarchies and processes controlling cellular differentiation and function. Moreover, organoids allow the pre-clinical testing of pharmacological substances, both from safety and efficacy standpoints …

Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma.

BACKGROUND: Recurrent nasopharyngeal carcinoma (NPC) remains a major challenge for clinicians and scientists. Tumor organoid is a revelational disease model that highly resembled the heterogeneity and histopathological characteristics of original tumors. This study aimed to optimize the modeling process of patient-derived NPC organoids (NPCOs), and establish a living-biobank of NPCs to study the mechanism and explore the more effective treatment of the disease. METHODS: Sixty-two fresh NPC tissue samples and 15 normal mucosa samples were collected for 3-dimensional (3D) organoid culture. The …

Porcine Intestinal Apical-Out Organoid Model for Gut Function Study.

Pig models provide valuable research information on farm animals, veterinary, and biomedical sciences. Experimental pig gut models are used in studies on physiology, nutrition, and diseases. Intestinal organoids are powerful tools for investigating intestinal functions such as nutrient uptake and gut barrier function. However, organoids have a basal-out structure and need to grow in the extracellular matrix, which causes difficulties in research on the intestinal apical membrane. We established porcine intestinal organoids from jejunum tissues and developed basal-out and apical-out organoids u…

Modeling Human Thyroid Development by Fetal Tissue-Derived Organoid Culture.

Euthyroidism is of profound importance for lifetime health. However, the early diagnosis or therapeutics of thyroid developmental defects has not been established, mainly due to limited understanding of human thyroid development and a lack of recapitulating research model. Herein, the authors elaborate the cell atlas and potential regulatory signaling of the evolution of heterogeneous thyrocyte population from 12 to 16 gestational weeks. Moreover, they establish a long-term culture of human fetal thyroid organoids (hFTOs) system, which retains the fetal thyroid lineages and molecular signature…

Development and characterization of patient-derived salivary gland cancer organoid cultures.

OBJECTIVE: Three-dimensional organoid cell cultures have been established for a variety of human cancers. For most rare cancers, including salivary gland cancer (SGC), these models are lacking, despite the great unmet need to study cancer biology in these diseases. Therefore, we aimed to develop patient-derived organoid (PDO) models for different subtypes of SGC. METHODS: Tumor samples of SGC patients were processed and embedded in Matrigel. Successful PDOs (expandable > 1*106 cells) were phenotypically characterized using immunohistochemistry (IHC) and genotypically by gene fusion analysis a

MECP2-related pathways are dysregulated in a cortical organoid model of myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is a multisystem, autosomal-dominant inherited disorder caused by CTG microsatellite repeat expansions (MREs … own. Here, we showed that CUG foci found early in the maturation of three-dimensional (3D) cortical organoids from DM1 patient-derived induced pluripotent stem cells (iPSCs) cause hyperphosphorylation of CUGBP Elav-like family member 2 (CELF2) protein. Integrative single-cell RNA sequencing and enhanced cross-linking and immunoprecipitation (eCLIP) analysis …

Human pancreatic tumour organoid-derived factors enhance myogenic differentiation.

BACKGROUND: Most patients with pancreatic cancer develop cachexia, which is characterized by progressive muscle loss. The mechanisms underlying muscle loss in cancer cachexia remain elusive. Pancreatic tumour organoids are 3D cell culture models that retain key characteristics of the parent tumour. We aimed to investigate the effect of pancreatic tumour organoid-derived factors on processes that determine skeletal muscle mass, including the regulation of muscle protein turnover and myogenesis. METHODS: Conditioned medium (CM) was collected from human pancreatic cancer cell lines (PK-45H, PANC…

[Organoids as a milestone on the way to personalized treatment of urothelial carcinoma: a systematic review].

BACKGROUND: The treatment options for locally advanced and metastatic urothelial carcinoma (UC) are currently limited to established chemoth … d to the databases used. RESULTS: Overall, 7 studies met the inclusion criteria on the topic of UC organoids. These studies describe the fundamental workflow in establishing organoid systems in patients with tumors of the urinary bladder or the renal pelvis. The success rates in generating organoids from non-muscle-invasive bladder cancer were 70-77% and f …

Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.

Cross-species comparison of drug responses at the organoid level could help to determine the human relevance of findings from animal studies. To this end, we first need to evaluate the in vitro to in vivo translatability of preclinical organoids. Here, we used 5-fluorouracil (5-FU) as an exemplar drug to test whether the in vivo gut response to this cytotoxicant was preserved in murine intestinal organoids. Mice treated with 5-FU at 20 or 50 mg/kg IV (low and high dose, respectively) displayed diarrhea at clinically relevant exposures. 5-FU also induced intestinal lesions, increased epithelial…

Salmonella enterica Infection of Human and Mouse Colon Organoid-Derived Monolayers.

Intestinal epithelial organoids reflect the morphology and function of an in vivo epithelial barrier. The composition of epithelial cell types reflects the cellular composition of the original tissue (small or large intestine) and organoids can be grown from different species. Thus, intestinal organoids constitute an ideal model to investigate infections of different hosts with enteric pathogens. In this chapter, we will focus on Salmonella infection of human and mouse colonoids grown in a 2D monolayer on permeable filter supports.

Organoid Models for Cancer Research-From Bed to Bench Side and Back.

Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapit…