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Prediction of the hypothalamus-pituitary organoid formation using machine learning.

Multi-cellular organoids are self-assembly aggregates that mimic biological functions and developmental processes of many tissue types in vitro. They are widely employed for disease modeling and functional studies. Hypothalamus-pituitary organoids can be generated through differentiation induction from pluripotent stem cells. However, their maturation is time consuming and labor intensive, and the quality of the resulting organoids can vary. Here, we developed a machine learning model capable of accurately predicting the successful generation of high-quality hypothalamus-pituitary organoids ba…

Endothelial specialization and angiocrine factors are critical for vascularized organoid models.

A vast network of vessels and capillaries is required in most organs because effective diffusion is typically limited to less than 200 μm. Most tissue engineering efforts have focused on re-creating vascularized networks to overcome this size barrier, but critically, the vasculature performs many other roles in development, homeostasis, disease, immune responses, and cancer via "angiocrine" interactions. Vascularized organoids will provide a new capability to test the importance of angiocrine interactions, which can be challenging to disentangle from their impacts on perfusion or substrate pro…

Применение и проблемы мозговых организмов при исследовании механизма заражения арбовирусом.

Арбовирусы, передаваемые кровососущими артроподами, являются причиной значительных заболеваний людей и животных, включая лихорадку, геморрагическую лихорадку и энцефалит, что создает серьезную угрозу для здоровья людей во всем мире. Тем не менее было затруднено проведение исследований по вопросу о механизмах арбовирусной инфекции и разработке терапевтических мер. Такая задержка объясняется прежде всего ограничениями, присущими текущим исследовательским моделям in vitro, включая клеточные культуры и животные. Простота типов клеток и межвидовых различий создает значительные препятствия для углуб

Совпадение в аннотации оригинала
Arboviruses, transmitted by blood-sucking arthropods, are responsible for significant human and animal diseases, including fever, hemorrhagi … understanding of arbovirus infection mechanisms and the development of effective drugs. Human brain organoids, derived from human pluripotent stem cells or human embryonic stem cells and cultured in three-dimensional systems, more accurately replicate the extensive neuronal cellular diversity and key characteristics of human neurodevelopment. These organoid …

Assessment of cytochrome P450 induction in canine intestinal organoid models.

Understanding cytochrome P450 (CYP) enzymes in the canine intestine is vital for predicting drug metabolism and developing safer oral medications. This study evaluates canine colonoids as a model to assess the expression and induction of essential intestinal CYP enzymes.Canine colonoids were cultured in expansion medium (EM) with Wnt-3A and in differentiation medium (DM) without Wnt-3A. We assessed the mRNA expression of CYP2B11, CYP2C21, CYP3A12, and CYP3A98 using qPCR and examined the effects of rifampicin and phenobarbital as inducers.Our findings show that DM significantly increased the mR

The Usefulness of Salivary Gland Organoids for Evaluation of the Potency of Botulinum Neurotoxin.

BACKGROUND AND OBJECTIVES: Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosm … We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT/A). We confirmed the expression of salivary gland-related genes and proteins using real-time polymerase chain rea …

3D Spheroid and Organoid Models to Study Neuroinfection of RNA Viruses.

Three-dimensional culture models of the brain enable the study of neuroinfection in the context of a complex interconnected cell matrix. Depending on the differentiation status of the neural cells, two models exist: 3D spheroids also called neurospheres and cerebral organoids. Here, we describe the preparation of 3D spheroids and cerebral organoids and give an outlook on their usage to study Rift Valley fever virus and other neurotropic viruses.

Visualization of Differentiated Cells in 3D and 2D Intestinal Organoid Cultures.

The intestinal epithelium maintains self-renewal and differentiation capacities via coordination of key signaling pathways, including the Wnt, bone morphogenetic protein (BMP), epidermal growth factor (EGF), and Notch signaling pathways. Based on this understanding, a combination of stem cell niche factors, EGF, Noggin, and the Wnt agonist R-spondin was shown to enable the growth of mouse intestinal stem cells and the formation of organoids with indefinite self-renewal and full differentiation capacity. Two small-molecule inhibitors, including a p38 inhibitor and a TGF-beta inhibitor, were add…

A human liver organoid screening platform for DILI risk prediction.

BACKGROUND & AIMS: Drug-induced liver injury (DILI), both intrinsic and idiosyncratic, causes frequent morbidity, mortality, clinical trial failures and post-approval withdrawal. This suggests an unmet need for improved in vitro models for DILI risk prediction that can account for diverse host genetics and other clinical factors. In this study, we evaluated the utility of human liver organoids (HLOs) for high-throughput DILI risk prediction and in an organ-on-chip system. METHODS: HLOs were derived from three separate iPSC lines and benchmarked on two platforms for their ability to model in v…

Towards a better understanding of diabetes mellitus using organoid models.

Our understanding of diabetes mellitus has benefited from a combination of clinical investigations and work in model organisms and cell lines. Organoid models for a wide range of tissues are emerging as an additional tool enabling the study of diabetes mellitus. The applications for organoid models include studying human pancreatic cell development, pancreatic physiology, the response of target organs to pancreatic hormones and how glucose toxicity can affect tissues such as the blood vessels, retina, kidney and nerves. Organoids can be derived from human tissue cells or pluripotent stem cells…

Recent advances in lung organoid development and applications in disease modeling.

Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms derived from various sources, including adult, fetal, and induced pluripotent stem cells, have now been generated, which more closely mimic the cellular architecture found within the airways and alveoli. In this regard, the establishment of novel protocols with optimized stem cell isolation and culture conditions has given rise to an array of models able to study key cellular and molecular players involved in lung injury and repair.

A BMP-2-triggered in vivo osteo-organoid for cell therapy.

Cell therapies and regenerative medicine interventions require an adequate source of therapeutic cells. Here, we demonstrate that constructing in vivo osteo-organoids by implanting bone morphogenetic protein-2-loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells including hematopoietic stem/progenitor cells (HSPCs), mesenchymal stem cells (MSCs), lymphocytes, and myeloid cells. Profiling of the in vivo osteo-organoid maturation process delineated three stages-fibroproliferation, osteochondral differen…

An in vivo neuroimmune organoid model to study human microglia phenotypes.

Microglia are specialized brain-resident macrophages that play crucial roles in brain development, homeostasis, and disease. However, until now, the ability to model interactions between the human brain environment and microglia has been severely limited. To overcome these limitations, we developed an in vivo xenotransplantation approach that allows us to study functionally mature human microglia (hMGs) that operate within a physiologically relevant, vascularized immunocompetent human brain organoid (iHBO) model. Our data show that organoid-resident hMGs gain human-specific transcriptomic sign

The mechano-chemical circuit drives skin organoid self-organization.

Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that the morphological transformation from multiple spheroidal units with morphogenesis competence (CMU) to planar skin is characterized by two abrupt cell motility-increasing events before calming down. The self-organizing processes are controlled by a morphogenetic module composed of molecular sensors, modulators, and executers. Increasing dermal stiffness provides the initial driving force (driver) which activates Yap1 (sensor) in…

The Roles of Extracellular Vesicles and Organoid Models in Female Reproductive Physiology.

Culture model systems that can recapitulate the anatomy and physiology of reproductive organs, such as three-dimensional (3D) organoid culture systems, limit the cost and welfare concerns associated with a research animal colony and provide alternative approaches to study specific processes in humans and animals. These 3D models facilitate a greater understanding of the physiological role of individual cell types and their interactions than can be accomplished with traditional monolayer culture systems. Furthermore, 3D culture systems allow for the examination of specific cellular, molecular,

Organoid Technology and Its Role for Theratyping Applications in Cystic Fibrosis.

Cystic fibrosis (CF) is a autosomal recessive, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembran … polation of disease modeling and individual drug response in vitro by producing mini organs called "organoids" easily obtained from nasal and rectal mucosa biopsies. In this review, we focus primarily on patient-derived intestinal organoids used as in vitro model for CF disease. Organoids combine high-validity of outcomes with a high throughput, thus enabli …

Progress in Modeling Neural Tube Development and Defects by Organoid Reconstruction.

It is clear that organoids are useful for studying the structure as well as the functions of organs and tissues; they are able to simulate cell-to-cell interactions, symmetrical and asymmetric division, proliferation, and migration of different cell groups. Some progress has been made using brain organoids to elucidate the genetic basis of certain neurodevelopmental disorders. Such as Parkinson's disease and Alzheimer's disease. However, research on organoids in early neural development has received insufficient attention, especially that focusing on neural tube precursors. In this review, we …

Media portrayal of ethical and social issues in brain organoid research.

BACKGROUND: Human brain organoids are a valuable research tool for studying brain development, physiology, and pathology. Yet, a host of potential ethical concerns are inherent in their creation. There is a growing group of bioethicists who acknowledge the moral imperative to develop brain organoid technologies and call for caution in this research. Although a relatively new technology, brain organoids and their uses are already being discussed in media literature. Media literature informs the public and policymakers but has the potential for utopian or dystopian distortions. Thus, it is impor…

Progenitor potential of lung epithelial organoid cells in a transplantation model.

Lung progenitor cells are crucial for regeneration following injury, yet it is unclear whether lung progenitor cells can be functionally engrafted after transplantation. We transplanted organoid cells derived from alveolar type II (AT2) cells enriched by SCA1-negative status (SNO) or multipotent SCA1-positive progenitor cells (SPO) into injured mouse lungs. Transplanted SNO cells are retained in the alveolar regions, whereas SPO cells incorporate into airway and alveolar regions. Single-cell transcriptomics demonstrate that transplanted SNO cells are comparable to native AT2 cells. Transplante

Epigenetic Drifts during Long-Term Intestinal Organoid Culture.

Organoids retain the morphological and molecular patterns of their tissue of origin, are self-organizing, relatively simple to handle and accessible to genetic engineering. Thus, they represent an optimal tool for studying the mechanisms of tissue maintenance and aging. Long-term expansion under standard growth conditions, however, is accompanied by changes in the growth pattern and kinetics. As a potential explanation of these alterations, epigenetic drifts in organoid culture have been suggested. Here, we studied histone tri-methylation at lysine 4 (H3K4me3) and 27 (H3K27me3) and transcripto…

Capture and metabolomic analysis of the human endometrial epithelial organoid secretome.

Suboptimal uterine fluid (UF) composition can lead to pregnancy loss and likely contributes to offspring susceptibility to chronic adult-onset disorders. However, our understanding of the biochemical composition and mechanisms underpinning UF formation and regulation remain elusive, particularly in humans. To address this challenge, we developed a high-throughput method for intraorganoid fluid (IOF) isolation from human endometrial epithelial organoids. The IOF is biochemically distinct to the extraorganoid fluid (EOF) and cell culture medium as evidenced by the exclusive presence of 17 metabo…