1051results about "Vascular endothelial cells" patented technology

The invention discloses a vascularized immune co-culture organoid chip for simulating a tumor microenvironment. The vascularized immune co-culture organoid chip comprises a chip main body and a bottom plate, a flow channel and a liquid storage tank are arranged in the chip main body; the runners comprise a first runner, a second runner, a third runner and a fourth runner; a compartment is arranged in the middle of the third flow channel; the first flow channel is connected with a first liquid storage tank which is used for injecting a first hydrogel suspension obtained by mixing fibroblasts and hydrogel into the first flow channel; the second flow channel is connected with a second liquid storage tank for injecting a culture solution into the second flow channel; a compartment is arranged in the middle of the third flow channel; the third flow channel is connected with a third liquid storage tank communicated with the compartment, and the compartment is connected with a compartment liquid storage tank; the compartment liquid storage tank is used for injecting a second hydrogel suspension obtained by mixing tumor organs and hydrogel into the compartment, and the third liquid storage tank is used for injecting hydrogel into the third flow channel; and the fourth flow channel is connected with a fourth liquid storage tank for injecting vascular endothelial cell and immune cell suspension into the fourth flow channel. The invention further discloses a vascularized immune co-culture organoid culture method for simulating the tumor microenvironment.

The invention provides a microfluidic chip, system and method for osteochondral organs, and relates to the technical field of organoid microfluidic chips, the chip comprises a bone microvascular endothelial cell channel, a bone compartment, a cartilage compartment and a synovial fluid channel which are arranged in parallel and in sequence, and permeation areas between the channel and the compartments and between the compartments. According to the scheme, the complex structure and function of a human osteochondral system are effectively simulated, the physiological and pathological processes of human bone joints can be simulated more truly in an in-vitro environment, and a method for establishing a highly-simulated femoral head necrosis model and osteoarthritis model based on the chip is provided. The problems that a traditional model is insufficient in physiological environment simulation, lack of control over dynamic culture conditions, tedious and time-consuming in the construction process, difficult to support high-throughput experiments and the like are solved.

The invention relates to the technical field of biological tissue engineering, and discloses a nerve-blood brain barrier co-culture model, which comprises a culture chip, and nerves and blood brain barriers respectively constructed in upper culture micropores and lower culture micropores of the culture chip. Wherein a semi-permeable membrane is arranged between the lower-layer culture micropores and the upper-layer culture micropores of the culture chip; the nerves are obtained by inoculating neurons / brain organs obtained by stem cell differentiation into the upper culture micropores for co-culture, and the blood brain barrier is obtained by inoculating brain microvascular endothelial cells obtained by stem cell differentiation into one side of the semipermeable membrane in the lower culture micropores for co-culture. The co-culture model is higher in biomimetic property, and can better simulate the structure and function of the blood brain barrier, for example, the co-culture model has a barrier function closer to the physiological level, the selective permeability of a small molecule drug is matched with the in-vivo permeation condition, and the co-culture model has the function of a small molecule related transporter. The invention further discloses a construction method and application.

The invention discloses hyaluronic acid / alginic acid dual-network hydrogel as well as a preparation method and application thereof. The hyaluronic acid / alginic acid double-network hydrogel comprises a first network and a second network which are not crosslinked with each other, and the first network and the second network are distributed in the hydrogel in an interpenetrating manner; the first network comprises an ionic cross-linked network of alginic acid with cell adhesion sites and calcium ions, and the second network comprises a chemical cross-linked network formed by covalent cross-linking of methacrylic anhydride modified hyaluronic acid. The hyaluronic acid / alginic acid double-network hydrogel disclosed by the invention is short in curing time, supports three-dimensional spreading of cells and formation of capillary lumens, has good mechanical stability, and has good application prospects in the aspects of three-dimensional culture of the cells, tissue engineering construction and the like.

The invention discloses for the first time pluripotent cells, including induced pluripotent stem cells, embryonic stem cells, hypo-immune pluripotent cells, cells that have been derived therefrom, and cells that have been biologically differentiated therefrom into particular tissue lineages that are ABO blood type O Rhesus Factor negative or otherwise evade rejection resulting from blood type antigen mismatch. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

A device for modelling physiological and pathophysiological states of the brain is provided. The device comprises a hydrogel with micropattern channels having a length, width and depth. The micropattern channels comprise cells selected from the group consisting of neurons, astrocytes, microglia, oligodendrocytes, neuronal organoids, cancer cells, cancer spheroids, brain tumoral cells and combinations thereof.

The invention discloses a novel application of an RNF6 gene, namely, an application of screening a medicine for preventing and / or treating Zika virus infection, aiming at inhibiting expression of the RNF6 gene or knocking out the RNF6 gene. A series of functional experiments prove that the RNF6 gene promotes the replication of the Zika virus, and the purpose of reducing the replication of the Zika virus can be achieved by using an expression inhibitor of the RNF6 gene or knocking out the RNF6 gene; experimental results show that the RNF6 gene can be used as a potential target for preventing and / or treating Zika virus infection, and a new direction is provided for development of drugs for preventing and / or treating Zika virus infection targeting the RNF6 gene in the future.

Type 2 diabetes (T2D) is a clinical syndrome caused by insufficient insulin secretion for insulin requirements. Described herein are compositions and methods for microphysiological MPS models of disease (MODs) for diabetes. These platforms allow one to compare the effect of chronic β-cell stimulation in the presence and absence of patient specific immune cells in IPSC-derived islets from each group. Additionally, one can reproduce the T2D β-cell phenotype, using islets-on-chips will also be exposed to gluco-lipotoxicity. Likewise, skeletal muscle-on-chips are exposed to patient specific activated immune cells, variable motor neuron innervation and lipids characteristic of T2D.

The invention discloses a vascularized tissue culture chip as well as a construction method and application thereof, and belongs to the technical field of biological tissue engineering and biological medicines. The vascularization tissue culture chip is formed by stacking five layers of sub-chips with different function requirements, a fluid channel and a culture chamber are formed, a highly integrated system is formed, and the design of a micro-column array further optimizes the fluid dynamic characteristics and reduces the dead angle effect of fluid. In-vivo microcirculation can be simulated, and a stable and controllable nutrition and metabolite exchange environment is provided for skin and liver tissue. The vascularized tissue culture chip provided by the invention provides a powerful research platform for a plurality of biomedical research fields such as personalized medical treatment, disease modeling, drug screening, toxicity testing, disease model research and the like.

The invention relates to the technical field of tumor biomedical engineering and organ chips, in particular to a vascularized gastric cancer organ chip and a preparation method thereof.The chip is composed of an integrated micro-fluidic main body, an annular micro-column array and an optical sealing film, and a central culture cavity is divided into a tumor area and a blood vessel area by micro-columns; the preparation method comprises the following steps: injecting a fibrous protein solution containing human umbilical vein endothelial cells and cancer-related fibroblasts into a vascular region, and adding thrombin for in-situ gelation to form a pre-vascularized network; the method comprises the following steps: mixing a patient-derived gastric cancer organ with a methacrylic acid esterified gelatin pre-polymerized solution, injecting the mixture into a tumor area, and carrying out photo-crosslinking immobilization; culturing for 7-14 days under the dynamic perfusion condition of a mixed culture medium to obtain a three-dimensional gastric cancer organ model containing a capillary network; the method is expected to be used for rapid, low-cost and high-throughput screening of chemotherapy or anti-angiogenesis drugs and accurate prediction of individual curative effects of patients.

Provided herein are compositions and methods for inducing an immune response in a subject, wherein the compositions comprise apoptotic cells, extracellular vesicles (EVs), and combinations thereof. Various compositions comprising mRNA encoding a microbial antigen are also provided. Further provided herein are compositions engineered to overexpress the human arrestin domain containing protein 1 [ARRDC1].

The invention discloses a filling and repairing agent for promoting angiogenesis and a preparation method thereof, the filling and repairing agent is composed of a vascular endothelial cell supernatant, acellular matrix particles, a suspending aid and a protective agent, the vascular endothelial cell supernatant is prepared by inducing vascular endothelial cells into a tube under a low-oxygen three-dimensional condition, collecting a cell culture solution, centrifuging and concentrating; the acellular matrix particles are obtained by acellular tissue matrix, shearing, freeze-drying, liquid nitrogen grinding and collecting; according to the filling repairing agent for promoting angiogenesis, the vascular endothelial cell supernate and the acellular matrix particles are combined, the filling repairing agent contains high-concentration angiogenesis-related factors and a stable three-dimensional bionic scaffold structure, function complementation is achieved through the synergistic effect of the bioactive factors and the bionic scaffold, and the filling repairing agent for promoting angiogenesis is obtained. Therefore, the filling repair agent which can promote angiogenesis, construct a physical support framework and promote tissue repair and regeneration capacity is innovatively obtained.

The invention relates to a cell collection method capable of simultaneously collecting three cells in a co-culture model, and belongs to the technical field of biology. The invention provides a cell collection method capable of simultaneously collecting three cells in a co-culture model, and the cell collection method comprises the following steps: after a three-cell co-culture model is constructed, taking out a Transwell chamber, retaining cells in the lower chamber, and collecting the cells in the lower chamber; respectively digesting the cells on the two sides of the Transwell cell membrane by using a trypsin solution with the concentration of 0.5 g / 100mL so as to respectively collect the cells on the two sides of the Transwell cell membrane. According to the cell collection method disclosed by the invention, the three cells in the three-cell co-culture model are simultaneously collected in a manner of digesting the cells on the two sides of the Transwell membrane step by step by using pancreatin, so that not only is the cell and consumable cost saved, but also the experimental synchronism of the three cells is ensured, and convenience is provided for optimizing the experimental process.

The invention discloses a pharmaceutical composition for promoting angiogenesis and tissue regeneration and application thereof. The pharmaceutical composition of the present invention comprises an acidic secretory protein rich in cysteine, a disaccharide chain proteoglycan, and an XV-type collagen alpha1 chain. The biological material system loaded with the three types of proteins can promote angiogenesis, and can improve the tissue regeneration efficiency of bone, cartilage and skin defect areas.

The present disclosure provides a preparation method and use of a hydrogel material for growth of blood vessel organoids (BVOs). The preparation method of the hydrogel material includes: (1) synthesis of gelatin methacryloyl (GelMA), and (2) synthesis of ns-GelMA-PEO. The hydrogel material may be used for in vitro cultivation of BVOs. The hydrogel material ns-GelMA-PEO prepared by the present disclosure may significantly improve the survival and budding abilities of BVOs. The ns-GelMA-PEO provides a novel solution for in vitro cultivation of BVOs, and may well support the growth and differentiation of organoids.

A method for constructing a microfluidic bone organoid-on-chip can continuously observe the impacts of different external factors on a bone tissue structure based on the “ternary regulation theory” of bone angiogenesis-bone resorption-osteogenesis coupling. The method includes: (1) building a visual three-dimensional cell cultivation platform to continuously observe impacts of different external factors on a ternary regulation theory based on angiogenesis of osteoclast precursors, osteoblasts and osteoclasts, such that a user is allowed to directly observe interactions among various kinds of cells; (2) designing microfluidic channels in a chip to allow a reagent involved to present a concentration gradient distribution in the chip; and (3) adding three bioinks including osteoblasts, osteoclasts and vascular endothelial cells respectively, so as to reflect the three cell components individually, in pairs, and as a whole in the chip. An apparatus for constructing a microfluidic bone organoid-on-chip is further provided.

The invention relates to the technical field of medical instruments, and discloses an application of a collagen-gelatin combined VEGF (vascular endothelial growth factor) mimic peptide in promoting growth of blood vessels, the collagen-gelatin combined VEGF mimic peptide is QKCMP-Enhancer, and the sequence of the collagen-gelatin combined VEGF mimic peptide is Ac-KLTWQELYQLKYKGI-(GPO) 5-(KR) 4-(RGD) 4-(KR) 4-GGG-(Gly) 3-NH2. The invention discloses a collagen-gelatin combined VEGF (vascular endothelial growth factor) mimic peptide which shows remarkable biological activity in the aspects of promoting angiogenesis, stimulating cell proliferation and inhibiting cell apoptosis. A new way and a new strategy are developed for treating related diseases; the collagen-gelatin is combined with the VEGF mimic peptide, so that a safer, more efficient and controllable angiogenesis method can be realized, and the collagen-gelatin combined VEGF mimic peptide has remarkable clinical application potential.

The invention relates to a blood flow connection type multi-organ chip capable of being freely assembled and reused, the blood flow connection type multi-organ chip comprises a chip cover body, organ culture chambers, a chip matrix and a pressure-sensitive film, the chip matrix comprises a plurality of groups of organ culture units which are mutually independent, each group of organ culture units comprises at least two culture flow channels and a plurality of organ culture holes, and the culture flow channels are communicated with the pressure-sensitive film. The organ culture holes are sequentially distributed at intervals along the culture flow channel, the bottom end of each organ culture hole is communicated with the culture flow channel, each organ culture hole is used for accommodating an organ culture chamber, the culture flow channel is located at the bottom of the chip substrate, one end of the culture flow channel is communicated with the storage pool, and the other end of the culture flow channel is communicated with the connecting port; the chip cover body is arranged at the top of the chip base body and completely covers the storage pools and the organ culture holes, the pressure-sensitive film covers the bottom of the chip base body to seal the culture flow channels, and in each group of organ culture units, a circulation path is formed between at least two culture flow channels through the storage pools. The biological function of the human body is better simulated, and disease modeling and treatment strategy research are carried out.

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 provides a construction method and application of a blood sinus networked liver organ. According to the method, pluripotent stem cells are co-differentiated into HAND1 < + > mesoderm and endoderm, a front intestine rear endoderm containing KDR < + > mesoderm progenitor cells is generated, a liver endoderm with CD34 < + > / CD31 < + > endothelial progenitor cells is generated, and the blood sinus networked liver organ is formed. The liver organ has a functional blood sinus endothelial network penetrating through the liver cluster, and has the characteristic functions of low-density lipoprotein uptake, human serum albumin removal, mediated secretion of blood coagulation factor 8 and the like. The method provides a new-generation highly bionic research tool for liver disease mechanism analysis, drug screening and regeneration repair.

The invention relates to the technical field of exosomes, in particular to application of astragalus membranaceus exosomes to cell protection in the vascular endothelial cell apoptosis process. According to the application, the astragalus membranaceus exosome and the abelmoschus esculentus exosome are extracted respectively, and the influence of the two exosomes on the vascular endothelial cell apoptosis process is compared, so that the result shows that the astragalus membranaceus exosome can protect cells in the vascular endothelial cell apoptosis process.

The invention discloses an RSV infection immortalized tree shrew aorta vascular endothelial cell model, and particularly relates to a method for separating and culturing primary aorta vascular endothelial cells from tree shrew aorta, further establishing an immortalized tree shrew aorta vascular endothelial cell line, taking the cell line as an RSV virus culture medium, and constructing an RSV infection immortalized tree shrew aorta vascular endothelial cell model. Establishing an RSV infected immortalized tree shrew aortic vascular endothelial cell model, and preparing a high-infection-titer RSV virus; the invention provides key support for preparation and detection of RSV virus and construction of a tree shrew in-vivo infection model, provides a stable virus source for development of comparative medical research or vaccine evaluation, and has far-reaching significance for deep exploration of RSV pathogenic mechanism, drug and vaccine evaluation and the like.

The invention belongs to the technical field of biomedical engineering and microfluidics, and particularly discloses a vascularized organ chip and method for large-scale culture, the vascularized organ chip comprises an upper runner layer and a lower culture layer, and the runner layer and the culture layer are fixedly sealed; a liquid storage pipe matched with the flow channel layer is adhered to the upper surface of the flow channel layer; according to the vascularized organ chip, the flow channel layer is used for pouring a culture solution to provide fluid stimulation and nutrients for cells; the three parallel-connected large-scale culture chambers of the culture layer are used for culturing cells, so that blood circulation of a microvascular system in a human body can be simulated, and a microenvironment in tissues can be reproduced more truly; meanwhile, the requirement for culturing a large number of tissue cells through the chip can be met, and the cell yield and the experiment scale can be effectively increased.

The invention relates to a pathological pulmonary fibrosis model and a construction method and application thereof. The pathological pulmonary fibrosis model provided by the invention is good in stability and controllability and high in maturity, not only can better simulate the function and structural characteristics of pulmonary alveoli-capillary barrier, but also has the pathological characteristics and immune microenvironment of pulmonary fibrosis lesions, has the advantage of high simulation degree, and has good application prospects in simulation and research of pulmonary fibrosis diseases. Good application prospects are realized in the aspects of drug detection, screening, evaluation, research and development and the like.

In various aspects, the invention provides culture platforms, cell culture media, and methods of differentiating pluripotent cells into hematopoietic cells. In certain aspects, the invention also provides pluripotent stem cell-derived hematopoietic cells generated using the media and methods disclosed herein. The pluripotent stem cell-derived permanent HE cells produced by the methods provided herein are capable of differentiating into hematopoietic lineage cells comprising T cell progenitor cells and T cells in addition to NK cell progenitor cells, NK cells, NKT cells, or B cells.

The invention discloses a bone organ chip loaded with a microelectrode array and a use method, and relates to the technical field of organ chips, the bone organ chip is made of a polydimethylsiloxane material, and the bone organ chip comprises a three-layer structure: a top layer, a middle layer and a bottom layer; the middle layer comprises two blood vessel micro-channels, two osteoblast micro-channels and a neuron micro-channel, the channels are separated through columns and micro-columns, and cell interaction in a bone micro-environment is simulated; a microelectrode array is arranged on the top layer and is used for monitoring electrical activity of neurons in real time; the bottom layer is provided with a pneumatic valve which can control opening and closing of the micro-channel. According to the invention, nerve and blood vessel channels are introduced, a nerve-blood vessel-immunoregulation bone microenvironment is constructed, physiological processes such as osteogenesis-blood vessel formation coupling and the like are embodied, intervals of different sizes can enhance intercellular crosstalk and allow blood vessels and neuron axons to selectively pass through, so that the chip can simulate a complex microenvironment of bone tissues, and the microenvironment of the bone tissues can be simulated; and an efficient and accurate in-vitro model is provided for bone disease mechanism research and drug development.

The invention discloses a preparation method and application of a novel hybrid extracellular vesicle. According to the invention, vesicles derived from endothelial cells and neutrophil cells are combined with deferoxamine, and a biological mixed nano vesicle platform (DFO (HEVS)) is developed to solve the problem of diabetes wound healing. According to the dual-targeting system, DFO is accurately delivered to a wound part by utilizing CXCR4 mediated endothelial cell homing and beta2 integrin dependent inflammation tropism, DFO (at) HEVs activates and recovers vascular regeneration through HIF-1alpha / VEGF, ferroptosis is inhibited through Nrf2 / GPX4 signal transduction, macrophages are reprogrammed into a repair promoting M2 phenotype, and oxidative stress-inflammation-ferroptosis circulation is effectively broken.

The invention relates to a retina nerve and blood vessel unit in-vitro three-culture model and a preparation method thereof, and belongs to the technical field of biology. The invention provides an in-vitro three-culture model of a retina nerve and blood vessel unit. The in-vitro three-culture model is obtained by carrying out in-vitro Transwell indirect co-culture on retina microvascular endothelial cells, retina ganglion cells and retina Muller cells. The in-vitro three-culture model of the retina nerve and blood vessel unit is based on a three-cell indirect co-culture method, retina microvascular endothelial cells, retina ganglion cells and retina Muller cells are simultaneously incorporated by utilizing Transwell, and the three cells are in indirect contact. The in-vitro three-culture model of the retina nerve and blood vessel unit can be used for more objectively simulating pathophysiological states of various cells of the retina nerve and blood vessel unit, so that common pathophysiological changes of mutual dependence and interaction of the three cells under in-vitro conditions can be observed.