179results about "Hepatocytes" patented technology

The application discloses a kind of hepatic organoids containing mesenchyme induction method, belong to organoid culture technical field.The method includes the following steps: (1) human embryonic stem cell WIBR3 pretreatment;(2) utilize human embryonic stem cell WIBR3 and induce liver organoids and mesenchymal cells;(3) mesenchymal cells and liver organoid cells are co-cultured, i.e. obtain the hepatic organoids containing mesenchyme.There is beneficial effect: the application changes the culture mode and method of the hepatic organoids containing mesenchyme.The hepatic organoids containing mesenchyme induction method proposed in the application is simple, and mesenchymal cells and other liver cells have the same genetic background source, suitable for the safety evaluation of drug and other chemical substances, liver fibrosis, non-alcoholic hepatitis modeling and pharmacodynamic evaluation.

The invention relates to the technical field of polypeptides, in particular to an enzyme-mimetic polypeptide, hydrogel, a preparation method and application, the enzyme-mimetic polypeptide selects a peptide fragment I and a peptide fragment II with biocompatibility and degradability as basic sequences, and the peptide fragment I and the peptide fragment II form a beta folding unit, so that the stability of a polypeptide structure can be enhanced; then, the peptide chain is driven to be self-assembled to form a regular nanofiber structure; according to the invention, the characteristic that the biomimetic polypeptide and metal ions are subjected to a complex reaction to form a chelate is utilized, the transparent and stable hydrogel can be rapidly formed without adding a gelatinizing agent, and TEM, SEM and rheological characterization are carried out on the hydrogel to find that the hydrogel containing the biomimetic polypeptide has a porous nanofiber network structure, so that the biomimetic polypeptide can be used for preparing the hydrogel. Meanwhile, the biomimetic polypeptide hydrogel has the same flexibility as natural tissues, and the characteristics indicate that the biomimetic polypeptide hydrogel is expected to have wide application prospects in the aspects of biomimetic materials, antibiosis, cell culture, drug carriers and the like.

The invention discloses a perfusion-free parallel double-cell intestine-liver chip system and application thereof in drug uptake evaluation, and belongs to the field of biomedical engineering and organ chips. The chip disclosed by the invention is simple in structure, free of an external pump and a complex pipeline, capable of realizing fluid circulation through swinging, convenient to operate, low in cost and small in pollution risk, and also capable of promoting cell differentiation and optimizing hepatocyte functions. The chip integrates a parallel intestinal cell and a liver cell which are communicated through a shared channel, can continuously simulate intestinal absorption and liver first-pass metabolism, and is closer to an in-vivo physiological state. The device adopts a detachable transparent modular design, can be repeatedly used, supports multi-group parallel operation, can improve experimental flux and result repeatability, and is suitable for in-vitro verification of drug absorption, permeability and metabolism evaluation.

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.

Systems and methods consistent with the present invention generally relate to microorganospheres (MOSs), and methods and apparatuses for forming and using MOSs. More particularly, in some embodiments, systems and methods consistent with the invention relate to the methods and apparatuses for forming and using MOSs generated from hepatocytes. MOSs that are generated from hepatocytes are suitable for testing liver toxicity and drug induced liver injury effects of various agents.

The invention relates to a cellulose-based hydrogel prepared based on a cellulose copolymer, a cellulose derivative copolymer or a blend thereof, ultramicro fibers of cellulose form a net structure, and the cellulose-based hydrogel has a highly-ordered three-dimensional micro-nano structure, is better in transparency and is more beneficial to observation of a cell state. The cellulose-based hydrogel is suitable for culture of 3D cell culture tissues and organoids, the stem cells cultured by the cellulose-based hydrogel can form cluster culture stem cells and organoids, the operation is simple, compact fused monolayer endoderm cells are formed, non-directional differentiation of the stem cells can be inhibited, and the formed organoids are thick in vesicle wall and are in a solid shape. And the obtained product is a differentiated mature organ and can be used for high-throughput drug screening, drug toxicity testing and regenerative medicine.

Featured here are methods for improving tissue or organ preservation and utilization through mitochondrial transplantation.

The present invention relates to specific liver microtissues comprising hepatocytes of at least three different phenotypes derived from induced pluripotent stem cells encapsulated in a single three-dimensional closed microcompartment. The present invention also relates to methods for preparing such liver microtissues and their use in the treatment or prevention of liver failure.

Production and maintenance of hematopoietic stem cells in in vitro culture systems has proven to be elusive. Disclosed herein are hematopoietic stem cell compositions that originate from organoids such as liver organoids. These organoids also comprise a rare type of immune cell that is not yet fully elucidated due to the difficulty in isolating said immune cell from biological samples. Also disclosed herein are methods of producing said hematopoietic stem cells and immune cells from organoids, as well as methods of expanding hematopoietic stem cells from other sources using these organoids.

The invention relates to the field of cell culture, in particular to a liver organ model culture device and method.The liver organ model culture device comprises a temperature control box and a box cover arranged on the temperature control box, a pressing column is slidably installed in the middle of the box cover in a penetrating mode, a column spring is wound around the outer side of the pressing column, and one end of the column spring is connected with the upper end of the pressing column; the other end of the column spring is fixed to the upper end of the box cover, a culture piece is arranged at the position, located on the inner side of the box cover, of the upper end of the temperature control box, a plurality of liquid changing holes are formed in the upper end of the box cover in a penetrating mode, a bearing frame is placed at the upper end of the box cover, and a plurality of liquid injection pipes are embedded in the bearing frame in a penetrating mode; a plurality of liquid suction pipes are embedded in the bearing frame in a penetrating mode, and the liquid injection pipes are located on the sides of the liquid suction pipes. According to the invention, the culture effect is improved, the liquid changing efficiency is also improved, and meanwhile, the gel matrix block is prevented from being damaged during liquid changing.

A novel method of inducing or producing hepatocytes from human induced pluripotent stem cells at an unprecedented efficiency and functionality. The core of the invention is the use of experimentally discovered mRNAs at multiple critical differentiation decision points along a pluripotent to mesendoderm to endoderm to hepatocytes pathway in a previously unknown manner.

The present disclosure provides porcine thymolivers, methods of making thereof, and methods of using thereof. The present disclosure further provides methods of treating a disease (e.g., a liver disease) in a human subject in need thereof comprising transplanting of a porcine thymoliver.

The present invention relates to methods for the in vitro production of a hepatocyte organoid from primary human hepatocytes (PHH). The present invention further relates to a cell culture system for the in vitro expansion of functional foetal, neonatal, paediatric and adult PHH and the mass generation of organoids and use of the cell culture system for the in vitro mass generation and expansion of functional adult PHH and / or formation of hepatocyte organoid.

A method for inducing conversion from non-hepatic stem cells or non-hepatic progenitor cells into hepatic stem cells or hepatic progenitor cells, which comprises introducing any of the following combinations into the non-hepatic stem cells or non-hepatic progenitor cells: (a) a combination of HNF1, HNF6 and FOXA; (b) a combination of HNF1 gene, HNF6 gene and FOXA gene; (c) a combination of HNF1, MYC and FOXA; or (d) a combination of HNF1 gene, MYC gene and FOXA gene.

This invention belongs to the field of hydrogel materials and relates to a method for preparing a hydrogel, comprising the following steps: dissolving bisphosphonic acid-modified pectin in water or an aqueous solution, adding a divalent metal cation solution to mix and obtain a precursor solution, adding a gelling solution to initiate cross-linking and form a hydrogel, wherein the gelling solution is a solution containing monovalent metal ions with a pH of 7-9. The hydrogel has broad application prospects in the field of ready-to-use reagents. Adding the precursor solution to a cell culture device and lyophilizing it can be used to prepare ready-to-use reagent kits. Dropping a cell suspension into the ready-to-use hydrogel reagent kit and adding cell culture medium yields a hydrogel encapsulated with cells for three-dimensional culture.

The invention provides an organoid culture medium, an organoid culture method and application of the organoid culture medium, the organoid culture medium comprises a first-stage culture medium, the first-stage culture medium comprises a first-stage basic culture medium and first-stage addition factors, and the first-stage addition factors comprise N-acetylcysteine, nicotinamide, a ROCK inhibitor, Noggin, R-spondin, EGF, HGF, Gastrin, FGF10, Blebbistatin, Forskolin, A83-01, LDN193189, DAPT, TGF-alpha and UDAC. By using the organoid culture medium, the liver organoid and the fatty liver organoid can be effectively obtained, and the obtained fatty liver organoid has obvious fat deposition, is sensitive to fatty liver treatment drugs, highly restores the physiological status when human body fatty liver diseases occur, and has high application value.

Disclosed herein are improved methods of expanding cell populations and methods of producing organoids from pluripotent stem cells, as well as compositions and uses thereof, compositions comprising liquid components that can be used to carry out these methods for supplementing amino acids, and kits comprising components for carrying out these methods and / or products of using these methods. These methods can be carried out without the need for xenogeneic and ambiguous basement membrane matrices for cell culture, which enables the achievement of good production specification (GMP) compliant methods for producing organoids for various uses such as clinical screening and treatment, methods for treating liver-related diseases or conditions and methods for screening candidate compounds or compositions for treating liver-related diseases or conditions are included.

A method for producing a metabolism-activated liver organ, comprising a step for culturing primary hepatocytes or hepatocyte-like cells in a differential medium to obtain a metabolism-activated liver organ, the differential medium is a medium containing a glucocorticoid receptor agonist and one or two selected from the group consisting of a growth hormone receptor agonist and a prolactin receptor agonist.

The present invention provides a biomaterial for immunomodulation comprising aggregates of phenotypically stabilized cells. Said biomaterial is meant to be preferentially administered in a limited location and provides immunomodulation for preventive or therapeutic purposes.It is also part of the present invention the process for production of the mentioned biomaterial and uses thereof. More specifically, the biomaterial for immunomodulation herein disclosed adds benefit in contexts of transplantation, chronic inflammation, autoimmune diseases, acute inflammation, cancer treatment, or in injured tissue regeneration.

The present application discloses cell clusters resembling the function and characteristics of endogenous pancreatic islets, and methods for making and using such cell clusters.

The invention provides a construction method of an HBV (Hepatitis B Virus) infection model based on multilineage hepatobiliary organs, which comprises the following steps: differentiating human pluripotent stem cells to form immune cell-containing hepatobiliary organs for further maturation culture, and enabling the hepatobiliary organs to be mature in function and highly express NTCP (Natriuretic Therapeutic Cells) by using a maturation culture medium containing bile metabolism substrate cholesterol and deoxybear bile acid, so as to obtain the HBV infection model based on the multilineage hepatobiliary organs. And then infecting the mature organs by adopting an HBV virus strain generated by HepAD38 cells to construct an in-vitro model which is susceptible to HBV and can maintain an infection state for a long time. According to the construction method, the liver infection and immune interaction microenvironment can be simulated more truly, and a stable and reliable experimental platform is provided for HBV infection mechanism research and anti-HBV drug screening.

The present application relates to a method for inducing liver oval cell line to form functional liver-like organ tissue on a liver acellular biological scaffold, belonging to the field of biotechnology, wherein the liver oval cell line (HOCL) is used as seed stem cells, and is implanted into a regenerative liver acellular biological scaffold (R-DLS) with biological activity; according to the in-vitro simulation of the development of a body-like liver organ microenvironment concept, a conditional culture solution capable of inducing HOCL liver function differentiation and reconstructing a functional liver organ structure is added, and a functional liver-like organ tissue is constructed in an in-vitro 3D culture system. In the method, the HOCL in the R-DLS shows its differentiation into functional hepatocytes in 2-24h in the in-vitro 3D culture system, and the liver-like organ tissue can be formed in 21 days. The "new liver" constructed by the method has important clinical conversion value for being used as a liver transplantation donor and treating ESLD.

The present invention relates to a method for the in vitro production of functional and proliferative hepatocytes and / or hepatocyte-like liver organoids (HELLOs). The present invention further relates to the hepatocyte-like liver organoids obtained via the present method and the use of said hepatocyte-like liver organoids in drug- and toxicity testing, and clinical trails.

The invention discloses application of dihydroartemisinin in construction of liver organoid, which is characterized in that by adding dihydroartemisinin into a liver organoid culture medium, the maturity of the liver organoid can be obviously improved, the maturity period is shortened, and the liver function characteristics (such as metabolic function and gene expression maturity) of the organoid are enhanced. The defects of an existing liver organ model in the aspect of simulating primary liver functions are effectively overcome, a more accurate in-vitro model is provided for research of liver related diseases, and a new platform and possibility are provided for development of liver regeneration and treatment methods.

To provide a technique for suppressing functional variations between a plurality of neural cell-containing spheroids across a plurality of lots or within a single lot.SOLUTION: The present invention relates to a cell-containing vessel comprising a plurality of neural cell-containing spheroids for which the variation calculated by the calculation method described below is less than 20%, where the neural cell-containing spheroids contain a plurality of types of cells including neural cells. (Calculation Method) Calcium transient assays are conducted for each of a plurality of neural cell-containing spheroids, a number of spontaneous oscillations per 10 minutes is measured, an average and a standard deviation for the number of spontaneous oscillations are calculated, and a variation is calculated by the following formula (1). Variation (%)=standard deviation for number of spontaneous oscillations / average number of spontaneous oscillations×100.SELECTED DRAWING: None

The invention features a method of producing aggregates of a plurality of cell populations (e.g., a first population of cells and a second population of cells). The method includes agitating a liquid medium that contains the cells in a bioreactor. These aggregates may be used for subsequent downstream applications, such as encapsulation in a biocompatible scaffold to form an engineered tissue construct.

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

The present invention relates to a method of culturing animal cells, preferably primary hepatocytes, comprising a first step of culturing the animal cells in non-adherent culture vessel, preferably a low or ultra-low attachment culture vessel, a second step of embedding the animal cells in a collagen matrix or in a gelatin matrix, and a third step of culturing the animal cells embedded in the collagen matrix or in the gelatin matrix, thereby obtaining 3D animal cell structures comprising proliferative animal cells, preferably spheroids comprising proliferative primary hepatocytes. The invention also relates to a spheroid comprising proliferative primary hepatocytes and the uses thereof for engineering an artificial liver model or an artificial liver organ, and for assessing in vitro the liver toxicity, genotoxicity and / or the effects of a drug or a compound.