808 results about "Organoid" patented technology

The invention provides a pourable tumor organoid vascularization model and a construction method thereof, and relates to the technical field of organoid culture. A temperature-sensitive degradable material and a photo-crosslinking modified temperature-sensitive material are used, the composite stent is printed through two channels, a multi-component gel mask partition curing process is combined, the stability of a perfusion pipeline is improved, and a partitioned highly-bionic complex microenvironment is accurately constructed in a macroscopic three-dimensional space; and constructing to obtain the perfusion tumor organ vascularization model. The model is high in bionic degree and stable in structure, can be applied to deepening cell and microenvironment interaction research and tumor-related drug screening, and has a good application prospect.

The invention provides an organoid drug reaction whole-course monitoring system, and relates to the technical field of data monitoring, and the system comprises an acquisition module which is used for acquiring a three-dimensional image sequence of an organoid at a set time interval, and monitoring the concentration data of metabolites in a culture solution to obtain multi-source monitoring data; the processing module is used for performing voxelization processing on the three-dimensional image sequence to form a time sequence three-dimensional voxel data set; and the calculation module is used for calculating barycentric coordinates of the organ-like structure based on the three-dimensional space distribution characteristics of the organ-like structure in the time sequence three-dimensional voxel data set, and establishing two mutually orthogonal space analysis axes in the maximum cross section of the organ-like structure by taking the barycentric coordinates as the center. According to the method, comprehensive and dynamic monitoring and evaluation of the organoid drug reaction process are realized through multi-source data collaborative acquisition, standardized spatial analysis, accurate form dynamic extraction, form and metabolism time sequence correlation modeling and real-time time sequence registration evaluation.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention belongs to the technical field of biology, and particularly relates to a high-throughput preparation method of a single-cell-derived organoid based on a microcapsule spherical shell structure, and the preparation method comprises the following steps: preparing an aqueous two-phase microcapsule encapsulated with a single cell, culturing the single cell in the aqueous two-phase microcapsule to obtain the organoid, the substances of the inner phase and / or the outer phase respectively comprise any one or a combination of more of the following substances: methacrylated gelatin, carboxymethyl cellulose, glucan, sodium alginate and polyvinyl alcohol. The invention also provides the organoid prepared by the preparation method and application of the preparation method. According to the invention, the microcapsule with a permeable core-shell structure is formed by packaging the microcapsule in a single-cell form in two-aqueous-phase liquid drops, the wrapping rate is effectively controlled and adjusted on the premise of conforming to Poisson distribution by optimizing parameters, and the single-cell wrapping rate and the organoid single-cell induction efficiency are optimized.

The invention relates to the technical field of image recognition processing, in particular to an automatic organoid labeling method based on machine vision and deep learning, which comprises the following steps: acquiring a to-be-processed image in a high-throughput culture environment, and preprocessing the image; inputting the preprocessed to-be-processed image into a preset digital image processing framework; the digital image processing architecture comprises an image filtering unit, a three-dimensional boundary reconstruction unit and a texture gray analysis unit; generating an independent target area mask through a three-dimensional boundary reconstruction unit; generating a high-density core mask through a texture gray analysis unit; based on the target area mask and the high-density core mask, constructing a three-dimensional geometric topological graph of the organoid; according to the method, the three-dimensional space morphological characteristics of the neighborhood nodes are obtained through processing by means of a numerical iterative aggregation algorithm, and the image feature parameters are output through analysis of the three-dimensional space morphological characteristics.

The invention discloses an application of imatinib mesylate in preparation of a targeted therapeutic drug for gastric signet ring cell carcinoma. The imatinib mesylate has an obvious inhibition effect on the growth of six patients with the pathological type of gastric signet-ring cell carcinoma, the inhibition effect is more obvious along with the increase of the concentration, the concentration and dosage dependency relationship is shown, and the half inhibitory concentration (IC50) is obviously smaller than that of a positive control drug apatinib. The medicine can play a targeted therapeutic role on the gastric signet ring cell carcinoma, and is small in toxic and side effects, economical, practical and low in cost.

Provided are chemically modified silk fibroin and a use thereof in cell and organoid culture. The chemically modified silk fibroin is a product obtained by sequentially carboxylating silk fibroin and modifying same by an organic amine having a phenol group. Also provided is a hydrogel based on the chemically modified silk fibroin. A hydrogel system has a hierarchical structure and mechanical properties similar to those of an extracellular matrix, and exhibits characteristics such as definite composition, controllable physicochemical properties, low cytotoxicity, good biocompatibility, and biodegradability, can support the growth and differentiation of cells and organoids, and is suitable as a matrigel for cell and organoid culture.

Disclosed are in vitro methods for the differentiation of precursor cells into a neural crest cell (NCC) primed to a neurogenic lineage. The methods may include, for example, the steps of activating a Hedgehog signaling pathway (“HH signaling pathway”) in a precursor cell, wherein the precursor cell may be contacted with a neural crest cell induction medium for differentiation of the precursor cell into a neural crest cell. Compositions for carrying out the disclosed methods are also disclosed.

The invention discloses a microfluidic multi-organ tumor chip targeted drug test AIGC system, and relates to the technical field of medical drug test information processing. The microfluidic multi-organ tumor chip targeted drug test AIGC system comprises a multi-omics data acquisition module for acquiring and preprocessing disturbance response data and dynamic expression data; the disturbance response pre-screening module is used for carrying out strength evaluation on drug action strength and reconstructing channel mapping; the characteristic space reconstruction module is used for performing action analysis on the whole medicine action state and dynamically adjusting a liquid medicine blending rule; the drug effect prediction module is used for predicting and evaluating the response degree of the organoid under the intervention of the specific drug and deducing the individualized drug effect intensity; and the feature augmentation self-closed loop module constructs a negative supervision signal and dynamically corrects a disturbance perception and feature embedding path. The problems that current multi-omics data is high in dimension, large in redundancy and large in noise, key features are difficult to extract under limited samples, and model generalization is difficult to maintain are solved.

The application discloses a construction method and application of a thymus organoid, and the method is used in combination with small molecule compounds and small molecule proteins to differentiate pluripotent stem cells into the thymus organoid under a suspension culture condition, and the method can efficiently obtain the thymus organoid which is closer to the natural thymus in structure and function.

The invention discloses a bone organ as well as a construction method and application thereof. According to the construction method of the bone organoid, in the in-vitro culture process of the bone organoid, a calcium source and a phosphorus source which are needed by mineralization are introduced into hydrogel and a culture medium, external force assistance is not needed, only single-type cells are used, simple ionized calcium and phosphorus are used, and microspheres are used for regulating and controlling spatial distribution of calcium and phosphorus; the in-situ mineralization method and the in-situ mineralization method are both beneficial for promoting mineralization osteogenesis of cells, osteogenesis, mineralization, cell layer formation, shaping and reconstruction are effectively guided through the in-situ mineralization mode, development of bone organs is promoted, the bone repair period is effectively shortened, and the method is safer and wider in applicability.

The present disclosure provides methods of making tissue-derived epithelial organoids. In particular, the present disclosure provides a tissue-derived epithelial organoid embedded in a hydrogel suspended in a culture medium. The present disclosure further provides methods of using such organoids.

Disclosed are methods for producing controlled endometrial organoids using micropatterning techniques, and methods for using endometrial cells or organoids for diagnostic and predictive purposes, and for optimizing IVF and other infertility-related treatments, including embryo transfer and intrauterine insemination (IUI). These organoids grow in a spatially controlled manner and exhibit less heterogeneity than organoids grown directly in a three-dimensional culture. The specification also describes methods for predicting the success of embryo transfer or other IVF-related treatments, optimizing embryo transfer, improving embryo implantation in the endometrium, and performing embryo transfer in subjects. These methods include culturing endometrial organoids or endometrial epithelial cells, and contacting the endometrial organoids or cells with one or more blast-like cells. In some embodiments, the endometrial organoids or cells include endometrial cells obtained from subjects undergoing or considering IVF-related treatment.

The invention provides a method and a system for determining operation nodes in an organoid culture process, and relates to the technical field of data processing, and the method comprises the following steps: carrying out interval division on a state track curved surface to obtain a plurality of physiological state intervals; performing convex hull algorithm calculation on the data point set in each physiological state interval, obtaining distribution boundary characteristics of the data points by constructing a minimum convex polygon, and obtaining morphological dynamics indexes based on the distribution boundary characteristics and change gradient calculation; performing normalization calibration processing on the monitoring data according to the morphodynamic indexes to obtain a calibrated growth state evaluation value; comparing the calibrated growth state evaluation value with a preset operation threshold value to obtain a comparison result; and determining an operation node of the organoid growth state based on a comparison result. According to the method, the operation node of the organoid culture can be accurately determined, and the controllability of the culture process and the stability of the growth state of the organoid are effectively improved.

The invention relates to the technical field of organoid culture, in particular to a pulmonary fibrosis organoid model and a construction method and application thereof. The pulmonary fibrosis organ-like model is obtained by co-culturing lentivirus stably transfected alveolar epithelial cells, human embryonic lung fibroblasts MRC-5 and macrophages. According to the invention, macrophages are innovatively introduced, a ternary co-culture system of lentivirus stably transfected alveolar epithelial cells, human embryonic lung fibroblasts MRC-5 and macrophages is constructed, and a key'epithelial injury-immune infiltration-fibroblast activation 'pathological triangle in a pulmonary fibrosis pathogenesis process can be more comprehensively simulated; the finally obtained pulmonary fibrosis organ-like model provides an efficient tool for pulmonary fibrosis mechanism research and research, development and screening of anti-pulmonary fibrosis drugs.

This invention relates to the application of ALKBH5 as a target in the preparation of drugs for inhibiting the progression of TNBC, and to the drugs themselves. This application discovers mRNA m 6 The alpha-modifying demethylase ALKBH5 is specifically highly expressed in triple-negative breast cancer (TNC). Using spontaneous TNC models and xenograft tumor models, knockout or knockdown of ALKBH5 significantly inhibited breast hyperplasia and the development of TNC, and promoted tumor differentiation. Simultaneously, the specific inhibitor EN300-14040 of ALKBH5 significantly inhibited the growth of TNC organoids, promoted TNC cell differentiation, and enhanced the sensitivity of TNC organoids to the endocrine drug 4OH-T, exhibiting a synergistic inhibitory effect with 4OH-T. Therefore, ALKBH5 represents a potential novel therapeutic target for TNC, and ALKBH5 inhibitors are a potential new type of drug for the treatment of TNC.

The present invention relates to a method for functionalizing a biopolymer having an -OH group or an -NH2 group by reacting the biopolymer with at least one compound having at least one C=C bond or C≡C bond and containing a chromophore that absorbs UV-Vis radiation directly adjacent to this bond. The present invention also relates to a method for obtaining a solid biopolymer material by reversibly crosslinking the functionalized biopolymer obtained by the above method under UV-Vis light irradiation. Furthermore, the present invention relates to the use of functionalized biopolymers as support materials for 3D bioprinting, or as materials for manufacturing structures selected from spheroids, organoids, artificial organs, coatings, and tissue models.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

Pancreatic cancer organoids prepared by a method of the present invention sufficiently reflect the interaction between cancer cells and endothelial cells, that is, cross-talk with the vascular niche, and thus they can show the characteristics of cancer-initiating cells (CICs) present in the organism environment, compared to conventional cancer organoids. Accordingly, the clinical applicability and reliability of the screened drug may be further remarkably increased.

The invention provides a management method and system for standardized organ-like sample library information, and is applied to the field of data processing application. The method comprises the following steps: preprocessing organoid sample source data and manufacturing process data to generate sample basic features, manufacturing process features and culture condition features; performing feature extraction processing on the quality control data to generate morphological features, molecular marker features, functional features, genome transcriptome features and vigor apoptosis features; processing the sample basic features, the manufacturing process features and the culture condition features based on a graph database model to generate an organoid data storage and association system; organoid generation and quality control processes are managed, key parameters and reagent batch numbers are recorded, operation is automatically triggered, data are associated, and standardized operation process records are generated; and processing the morphological characteristics, the molecular marker characteristics, the functional characteristics, the genome transcriptome characteristics and the vigor apoptosis characteristics to generate an organoid quality evaluation result.

This invention relates to the field of organoid disease models, and discloses a method for constructing a human brain organoid model of early-onset Alzheimer's disease (AD) and its applications. This invention introduces [a specific technology] into human embryonic stem cell lines through single-base editing and lead editing techniques. PSEN1 ΔE9、 PSEN1 M146V and APP Human embryonic stem cell lines carrying four familial pathogenic gene mutations (K670N and M671L) were constructed and induced to differentiate into Alzheimer's disease (AD) brain organoids. The AD brain organoid model established by this invention exhibited tau phosphorylation pathological phenotypes as early as 20 days and Aβ-related phenotypes as early as 40 days, with increased total Aβ, decreased Aβ42 / Aβ40 ratio, and simultaneous aggravation of Aβ-Tau pathology. This represents a complex neurodegenerative pathological model where multiple mutations synergistically regulate Aβ production and tau phosphorylation, which is highly valuable for understanding and studying early-onset familial AD. This invention provides a human brain organoid model for in vitro AD studies and offers a tool for studying the pathological mechanisms of AD and screening drugs.

The invention discloses an organ-like drug resistance prediction method and device and a storage medium, and relates to the technical field of bioinformatics, and the method comprises the steps: S1, constructing an initial prediction model; s2, acquiring a training data set; s3, training an optimization prediction model; s4, acquiring related data of a to-be-predicted drug; s5, obtaining a prediction result of the drug resistance of the to-be-predicted drug; according to the method, the drug resistance of the organoid to the drug can be predicted more accurately. By fusing multi-dimensional features of gene mutation, target mutation and drug functional groups, the understanding and learning ability of the model to the drug resistance mechanism is enhanced, and the reliability of drug resistance prediction is improved. The method not only can accurately capture key information of influence of gene and target mutation on drug resistance, but also can highlight unique mutant genes of the organoid on drug resistance by comparing feature differences of the organoid and a common cell line, so that an efficient and accurate calculation framework is provided for drug resistance detection.

The invention belongs to the cross technical field of veterinary medicine and biomedicine, and relates to a construction and evaluation method of a dog spontaneous breast cancer organoid model, which specifically comprises the following steps: (1) obtaining dog spontaneous breast cancer tissues through operation or biopsy, separating tumor tissues under sterile conditions, and carrying out fine enzymolysis digestion treatment to obtain dog spontaneous breast cancer tissues; obtaining a single-cell suspension; and (2) inoculating the single-cell suspension into a three-dimensional culture system, carrying out three-dimensional culture by adopting a culture medium containing EGF, FGF and B27 in combination with a growth factor, promoting the growth and amplification of the breast cancer organs, and carrying out timely passage according to the growth condition so as to maintain the activity of the model. The model constructed by the invention completely retains genetic heterogeneity and pathological microenvironment of primary tumors, does not need gene editing, is simple and convenient to operate and low in cost, is particularly suitable for individual drug sensitivity detection of pet dogs, and provides an efficient and high-simulation experimental platform for dog breast cancer mechanism research and clinical precise medication.

The present application relates to a method for constructing a human acute liver injury and chemotaxis model based on a normal liver organoid and application thereof. Specifically, the present application provides a method for constructing a human liver organoid; further, contacting the liver organoid with a hepatotoxic drug can construct a human acute liver injury model; co-culturing the organoid or the injury model with immune cells can construct an in vitro immune cell chemotaxis model. The present application also provides reversible immunoaffinity magnetic beads for isolating VSIG4-positive macrophages and a method for isolating the same. The human liver organoid, acute liver injury model and chemotaxis model of the present application can be used for screening drugs for treating acute liver injury, evaluating the hepatotoxicity of compounds, researching the pathogenesis of acute liver injury and evaluating the effect of immunomodulatory drugs.

Methods for producing prevascularized organoids, and compositions comprising such prevascularized organoids, are provided. Methods of treating ischemic conditions and promoting angiogenesis by administering the prevascularized organoids to a subject in need thereof are also provided.

The utility model relates to the technical field of micro-fluidic chips, and provides an organ-like culture chip which comprises a first substrate and a second substrate, and the first substrate and the second substrate are overlapped; the first substrate is provided with a first cavity, the first cavity is used for accommodating organoid cells, the second substrate is provided with a second cavity, the second cavity is communicated with the first cavity, and the second cavity is used for accommodating a cell culture medium; a liquid injection runner is arranged on the periphery of the second cavity and is used for flowing a detection medicine and a blood simulant, and a semi-permeable membrane is arranged between the liquid injection runner and the second cavity for substance exchange. According to the organoid culture chip, the liquid injection flow channel is arranged around the second cavity, and the semi-permeable membrane is arranged between the second cavity and the liquid injection flow channel, so that organoid cells and blood simulants can be subjected to material exchange through the semi-permeable membrane so as to simulate a blood brain barrier, and the application of the micro-fluidic chip in the aspect of brain-like organs is realized.

A method of treating male hypogonadism in a subject in need thereof includes administering to the subject testicular organoids generated from isolated male progenitor cells. The method can be used to slow or halt the progression of age-related diseases, and increase healthspan and longevity, in hypogonadal males. The method can be used with subjects that have not or are not receiving testosterone replacement therapy. The method does not require that the subject is pre-treated with CG. The testicular organoid includes cells expressing GFRA1, VEGF, VEGFR2, PDGF-Rα, Cyp11A1, 3β-HSD, 17β-HSD, LHCGR, α-SMA, CD11b, MHC CII, CD64, CD95, Sox9, AR, inhibin β-B, and FSHR.

This document provides a method for generating human heart organoids (hHO) with integrated macrophages (MPs), the method comprising adding monocytes to a first culture medium containing hHOs, wherein the hHOs have been differentiated for at least 5 days, and agitating the hHOs, monocytes, and the first culture medium or fresh culture medium to generate hHOs with integrated MPs. hHOs with integrated MPs prepared by the disclosed method are also provided.

The application provides a pulmonary artery tissue-derived cell, an organoid and a construction method and application thereof. The pulmonary artery intimal stripping tissue organoid structure obtained by the preparation method is clear, has consistent cell types as the source tissue, is close to the original tissue, is convenient for researchers to operate, and thus has good practical application value.