172 results about "Hematopoietic cell" patented technology

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.

Provided herein are genetically modified hematopoietic cells with reduced expression or activity of: (i) one or more CRL5 complex genes, and / or (ii) one or more genes orthogonal to the CRL5 complex, that exhibit improved therapeutic potential compared to wild-type hematopoietic cells, as well as methods of generating and using genetically modified hematopoietic cells for the treatment of a disease, such as cancer.

Provided herein are methods and compositions for genetically engineering a cell (e.g., a hematopoietic cell) using CRISPR / Cas systems and homology-directed repair, genetically engineered cells produced by such methods, and methods involving administering such genetically engineered cells to a subject, such as a subject having a genetic disease.

The present disclosure relates to methods of conditioning and / or depleting cell populations in the bone marrow of a subject in need of hematopoietic cell transplantation (HCT), comprising administering an antibody that binds to a target on endogenous hematopoietic stem cells (HSCs) in the subject. In a preferred embodiment, the target is CD 117 (c-kit).

The invention provides a system that comprises pharmaceutical agents for use in immunotherapy for reducing the side-effects of an antigen-recognizing receptor against antigen-expressing non-target cells in an individual. The system includes an antigen-recognizing receptor that specifically recognizes an antigen on target cells and at least on one hematopoietic cell type in the individual. The antigen-recognizing receptor is exemplified by chimeric antigen receptors (CAR) be expressed on the surface of an immune effector cells. The system also includes hematopoietic cells resistant to recognition of the same antigen by the antigen-recognizing receptor.

A method of generating a hematopoietic cell, including providing a source cell and treating the source cell with a metabolic regulator that directs the source cell to preferentially use glycolysis or oxidative phosphorylation and / or cholesterol biosynthesis, wherein the source cell is differentiated into a GPA+ erythroid cell or a CD45+ non-erythroid cell. In some examples, the source cell is selected from the group consisting of a hemogenic endothelial (HE) cell, a iPS cell such as a differentiating iPS cell, a cell directly reprogrammed to a known pre-cursor of a hematopoietic cell, a cell directly reprogrammed to a hematopoietic cell or precursor of a hematopoietic cell, a reprogrammed cell that is subsequently further reprogrammed to a hematopoietic cell or precursor of a hematopoietic cell, an adult hematopoietic cell derived from bone marrow or mobilized peripheral blood and a neonatal hematopoietic cell derived from cord blood or prenatal tissue (e.g. placenta). Some examples involve metabolically regulating a lipid biosynthesis pathway with an inhibitor of the lipid biosynthesis pathway or metabolically regulating a histone acetylation pathway with an inhibitor of the histone acetylation pathway.

Provided herein are polypeptide compositions and chimeric antigen receptors comprising natural ligands of hematopoietic cell receptors and are thereby able to specifically bind to hematopoietic cell receptors. Also provided are methods and compositions for using the polypeptide compositions and chimeric antigen receptors in the treatment of disease, such as cancer, for editing a gene in a cell, and for culturing populations of cells.

The invention provides a preparation method and application of a red blood cell lysis buffer for Rh double-group typing. The preparation method comprises the following steps: (1) preparing a stock solution 1; (2) preparing a stock solution 2; (3) mixing the stock solution 1 with H2O to obtain an application solution 1; (4) preparing application liquid 2; (5) adding 50 [mu] L of to-be-detected sample near-albuginea layer hematopoietic cells into 1 mL of the application liquid 1, and uniformly mixing; (6) centrifuging the mixed solution obtained in the step (5), and discarding the supernate; washing with normal saline under the condition of 1000g each time, and centrifuging; discarding supernate, dripping 2-3 drops of normal saline, and uniformly mixing; and (7) adding one drop of erythrocyte suspension and one drop of corresponding antibody into the blank card, and centrifugally observing the result. According to the preparation method of the red blood cell lysis buffer for Rh double-group typing, the detection rate is high, the preparation method is simple, the cost is low, and the red blood cell lysis buffer is very suitable for being popularized and popularized in primary medical institutions.

The invention discloses a gene combination for risk prediction of acute graft versus host disease and donor screening before hematopoietic cell transplantation and application of the gene combination. According to the present invention, the gene combination with the post-transplantation aGVHD occurrence prediction and diagnosis value is found through the whole genome sequencing and the target gene capture sequencing method; on one hand, comprehensive judgment and evaluation are carried out by detecting gene combination mutation conditions of donors and recipients, selection of transplantation donors is optimized, and the survival rate and the survival quality of patients are improved; on the other hand, the occurrence of aGVHD after transplantation of the recipient can be predicted by detecting the gene combination mutation condition of the donor and the recipient, and a basis is provided for potential aGVHD diagnosis; and thirdly, a new genetic basis is provided for revealing the pathogenesis of the aGVHD, and a new drug target is provided for treating the aGVHD.

It is an object of the present invention to provide transport microcapsules that are ingested by a target cell type and permanently or temporarily alter the target cell without thereby causing a toxic effect on the cell. The solution according to the invention consists in the use of a monodisperse core to thereby produce polyelectrolyte nanocapsules having cell-specific dimensions, in which the dimensions for hematopoietic cells range from 20 to 80 nm, preferably from 40 to 60 nm. The size of the particles must be in a very narrow range to prevent the occurrence of toxic effects. In order to maintain the low toxicity of nanomicrocapsules, it is also important to remove nanoparticles (cores) surrounding which create microcapsules prior to use. The method for this purpose is known in the prior art (e.g., using EDTA removal). Another object of the invention is the stabilization of transport microcapsules. The solution according to the invention consists in modifying microcapsules, layers and / or carriers to be packaged by functional groups, allowing stabilization and thus long-term storage at room temperature. The third purpose of the invention is targeted introduction of transport microcapsules. The solution according to the invention is functionalization of the layer by chemical modification and / or supplementation of the layer with antibodies, proteins or peptides.

The application relates to an image-based marrow component segmentation method and system, comprising the following steps: acquiring an original marrow biopsy digital image and preprocessing, obtaining a hematopoietic cell tissue and bone trabecula Mask mask image based on the preprocessed image; based on the original marrow biopsy digital image, sequentially performing color channel conversion, morphological open operation, isolated point elimination and hole filling to obtain a bone trabecula Mask mask image; based on the preprocessed image, obtaining a fat cell tissue Mask mask image according to the morphological characteristics of fat cells; and according to the obtained bone trabecula Mask mask image, the bone trabecula and hematopoietic cell tissue Mask mask image and the fat cell tissue Mask mask image, obtaining the area proportion of the bone trabecula, the hematopoietic cell tissue and the fat cell tissue in the original marrow biopsy digital image in each image.

The present disclosure relates to anti-human CD154 antibodies having a modified effector function. The present disclosure also relates to the use of these anti-human CD154 antibodies in the treatment of conditions associated with CD154 activation, the conditions associated with CD154 activation are, for example, transplant rejection, inflammatory conditions and diseases, dysfunctional immune responses associated with viral infections and diseases, autoimmune conditions and diseases, allergic conditions, atherosclerotic conditions, or neurodegenerative conditions and diseases. The present disclosure also relates to the use of these anti-human CD154 antibodies in inducing central tolerance and hematopoietic cell chimerism in transplanted patients.

The present invention discloses an engineered cell and its application, wherein the engineered cell lacks or reduces the expression of HLA-A protein and / or HLA-B protein compared with the wild type. The engineered cell disclosed in the present invention can significantly reduce the immune rejection reaction after human hematopoietic cell infusion, while significantly improving the implantation rate and long-term reconstruction capacity in vivo. The cell will significantly expand the use of existing cord blood and bone marrow donor banks, reduce the need to recruit a large number of donors to match recipients, increase the probability of HLA matching donors, and thus expand the infusion of clinical-grade allogeneic cells. As a source of universal cells, engineered cells can realize HLA-matched off-the-shelf cell therapy, which has important prospects for clinical transplantation treatment.

The present invention provides methods and compositions for treating cancer in a subject comprising the use of therapeutic cells and compositions to prevent or reduce T cell exhaustion. Modified hematopoietic cells comprising a genomic modification in an enhancer surround the GAB3 gene are also provided.

The application discloses a method for establishing a mouse model of MHC haplotype compatible allogeneic hematopoietic cell transplantation, and belongs to the technical field of animal experiment model construction. The technical problem to be solved by the application is how to construct a mouse model which can be used to study the immune reconstruction mechanism and treatment effect evaluation of MHC haplotype compatibility and MHC full compatibility in bone marrow cell transplantation recipient mice. To solve the technical problem, the application provides a method for constructing a mouse model of MHC haplotype compatible allogeneic hematopoietic cell transplantation, which comprises transplanting bone marrow cells of a donor mouse into a recipient mouse, and the MHC haplotype of the donor mouse and the recipient mouse is compatible. The application sets a modeling condition, and the model establishment condition is evaluated by survival condition, graft-versus-host disease and rejection reaction observation, flow cytometry and histopathological section, so as to prove that the model is reliable and stable.

The present disclosure relates to methods, media and supplements for culturing target cells, such as hematopoietic stem and progenitor cells (HSPC). The methods, media, and supplements of the present disclosure may include one or more epigenetic modifiers within culture conditions to culture and / or expand target cells, such as HSPC or CD34 + cells, such as may be obtained, enriched, or isolated from infected / diseased or normal primary samples. Output populations of HSPCs amplified in the presence of one or more epigenetic modifiers may be suitable for use in downstream applications.

Methods and compositions disclosed herein generally relate to compositions and methods for suppressing hematopoietic stem and progenitor cells (HSPCs) and the treatment of diseases or disorders involving UBE2N, such as cancers, including disorders such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and chronic inflammatory disorders. Particular aspects relate to treating, e.g. acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5). Particular aspects of the invention relate to determining an individual in need of treatment who can be treated with a UBE2N inhibitor, such as an individual having AML-M4 and / or AML-M5. The invention further relates to using a UBE2N inhibitor to treat a disease or disorder characterized by malignant hematopoietic cells, as well as other cancers, and chronic inflammatory disorders, and as immune checkpoint regulators.

When a cancer patient is administered an anti-cancer therapy targeting a lineage specific cell-surface antigen (e.g., CD33 (Siglec-3), CLL-1, CD123, CD327 (Siglec-6), and / or CD312 (EMR2)), e.g., in the form of an immunotherapeutic agent, the therapy can 15 deplete not only cancer cells expressing the lineage-specific cell-surface antigen, but also noncancerous cells expressing the lineage-specific cell-surface antigen in an "on-target, off tumor" effect. This disclosure provides, e.g., novel cells having a modification (e.g., insertion or deletion) in an endogenous lineage-specific cell-surface antigen (e.g., CD33 (Siglec-3), CLL-1, CD123, CD327 (Siglec-6), and / or CD312 (EMR2)) gene. The disclosure also provides compositions, e.g., gRNAs, that can be used to make such a modification.

The invention relates to the technical field of hematopoietic reconstruction, in particular to application of costal cartilage derived stem cells and costal cartilage derived stem cells combined with pluripotent progenitor cells, hematopoietic stem cells or cyclosporine in preparation of a preparation for hematopoietic reconstruction. The costal cartilage derived stem cells (CD45-CD51 +) are derived from costal cartilage and have remarkable ecological niche recovery capability. When the cells are used alone or combined with hematopoietic stem cells and pluripotent progenitor cells, the hematopoietic function can be enhanced. The costal cartilage-derived stem cells are directionally differentiated into important supporting cells forming bone marrow ecological niche, secrete hematopoietic cell factors and protect hematopoietic stem / progenitor cells. In treatment of aplastic anemia, costal cartilage-derived stem cells and cyclosporin A have a synergistic effect, and immune-mediated bone marrow failure is improved through dual mechanisms. According to the technical scheme, the technical problem that the effect of treating bone marrow failure and promoting hematopoietic reconstruction by hematopoietic stem cell transplantation is not ideal is solved, and a new way is opened up for treating bone marrow failure and blood system diseases.

The invention provides a system that comprises pharmaceutical agents for use in immunotherapy for reducing the side-effects of an antigen-recognizing receptor against antigen-expressing non-target cells in an individual. The system includes an antigen-recognizing receptor that specifically recognizes an antigen on target cells and at least on one hematopoietic cell type in the individual. The antigen-recognizing receptor is exemplified by chimeric antigen receptors (CAR) be expressed on the surface of an immune effector cells. The system also includes hematopoietic cells resistant to recognition of the same antigen by the antigen-recognizing receptor.

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

The present disclosure provides use of a hematopoietic cell kinase (HCK) inhibitor in preparation of a drug for treating pulmonary fibrosis, and relates to the technical field of biomedicine. In the present disclosure, idiopathic pulmonary fibrosis (IPF) model mice are used as a subject to allow research. Administration of an HCK inhibitor RK-20449 to IPF mice can effectively alleviate the progression of pulmonary fibrosis. A weight and a survival rate of the IPF mice have improved to a certain extent, and their lung function has improved significantly. The transcription levels of inflammatory factors Il-1β, Il-6, and Tnf-α in a lung tissue of the IPF mice have decreased, while the concentrations of inflammatory factors IL-1β and IL-6 in the alveolar lavage fluid have also decreased. The transcription levels of fibrosis factors Col-I and Fn-1 are decreased, the collagen-specific amino acid hydroxyproline is decreased, and the degree of lesions is alleviated.

The invention discloses a diagnosis marker for diabetes complicated with atrial fibrillation and application of the diagnosis marker, and relates to the technical field of biological medicine. The diagnostic marker is hematopoietic cell kinase (HCK). The invention finds that HCK can effectively predict the occurrence risk of diabetes mellitus combined with atrial fibrillation and provide an effective treatment target for diabetes mellitus combined with atrial fibrillation. The invention verifies that the knock-down HCK can effectively inhibit AGEs-induced HL-1 cell CaMKII phosphorylation, myocardial fibrosis, mitochondrial membrane potential damage and ROS generation, and alleviates the inhibition effect on AMPK / mTOR signal channel activation, thereby reducing the atrial fibrillation susceptibility. The invention also proves that the risk (AUC is 0.853) of the diabetic with atrial fibrillation can be accurately identified by detecting the HCK level in the plasma. The invention provides a new medical approach for early risk assessment and targeted intervention of diabetes mellitus combined with atrial fibrillation.

Disclosed herein are IL-4 cytokine compositions with enhanced biological activity having increased selectivity for IL-4 cytokine receptors, and methods for their use. These compositions encompass interleukin-4 (IL-4) muteins. The disclosed methods encompass administering an IL-4 to treat neoplastic diseases, autoimmune diseases, infectious diseases or for expanding a hematopoietic cell population.

This invention provides an in vitro method for generating hematopoietic cells, the method comprising: a) providing cells genetically modified to contain nucleotide sequences encoding exogenous transcription factors, said exogenous transcription factors including ETS family transcription factors, T-cell acute lymphoblastic leukemia protein 1 (Tal1), and GATA family transcription factors, wherein expression of the exogenous transcription factors derived from said nucleotide sequences can be induced by co-culturing with an inducer, and wherein said cells contain exogenous transcription factors at detectable expression levels; and b) culturing the genetically modified cells in a differentiation medium without an inducer, such that the expression level of said exogenous transcription factors in said cells is reduced to a level that allows the cells to differentiate into hematopoietic cells. Genetically modified hematopoietic cells, genetically modified cells, and their therapeutic uses are also provided.

The present invention discloses a tissue regeneration promoting and blood enriching holographic organic food material nutritional diet formula and a production process and application thereof, the tissue regeneration promoting and blood enriching holographic organic food material nutritional diet formula comprises a drink and a food which are matched for eating, and the drink comprises 4 g of dried small shrimps, 4 g of wheat bran, 20 g of soybean meal, 3 g of kelp, 5 g of Chinese chestnut powder, 7 g of buckwheat, 2.5 g of Chinese yam powder, 2.5 g of laver, 2 g of salt and 200 g of water; the food comprises 3 g of Brazil chestnuts, 10 g of walnut kernels, 10 g of sunflower seed kernels, 10 g of peanut kernels, 10 g of pine nuts, 14.5 g of wheat flour, 10 g of sweet potato powder, 10 g of potato powder, 10 g of corn flour, 1 g of pseudo-ginseng, 3 g of astragalus membranaceus, 3 g of angelica sinensis, 2 g of fructus lycii, 1.5 g of bletilla striata and 2 g of salt. According to the present invention, the nutrient ratio matching is reasonable, the food material variety is diversified, the food material ratio is balanced, all essential nutrients and a large amount of active biotin can be provided for the human body, the immunity and the self-healing ability are improved, the hematopoietic function is promoted, the hematopoietic cells are promoted, and the resistance of the human body is improved; the product is convenient to manufacture, free of chemical components and harmful substances and meets the hygienic standard.

The invention relates to a Chinese herbal medicine pigeon pea leaf. Research shows that the pigeon pea leaf can improve chronic myelosuppression caused by methotrexate (MTX). Results of animal experiments show that blood analysis results show that liver and kidney functions are normal after administration of pigeon pea leaves; after treatment, the number of red blood cells and white blood cells and the level of hemoglobin are remarkably improved, and after treatment of a pigeon pea leaf high-dose group (0.81 g / ml), the level of platelets (PLT) is remarkably increased. In addition, a thighbone marrow smear experiment result shows that compared with a blank group, hematopoietic cells are increased after the pigeon pea leaves are used for treatment. In general, the pigeon pea leaves can significantly improve bone marrow injury caused by MTX, and the curative effect of the pigeon pea leaves is superior to that of folic acid (FA) in a positive control group. Therefore, the pigeon pea leaf has an obvious protective effect on chronic myelosuppression caused by methotrexate, and shows relatively high safety.

The disclosure provides anti-CD74 antibodies, anti-CD74 antibody conjugates, compositions, and their use in reducing a population of hematopoietic cells.

The invention provides a method of producing a population of CD34+ hematopoietic precursor cells. The CD34+ hematopoietic precursor cells are used in methods of producing natural killer (NK), methods of inducing NK cell differentiation from pluripotent stem cells (PSCs), and methods of generating terminally differentiated hematopoietic cells from PSCs. The differentiation of immune cells such as NK cells from PSCs includes the use of a hemogenic endothelium induction cocktail that includes a WNT signaling pathway activator, a bone morphogenetic protein and / or a vascular endothelial growth factor. Also provided is a method of producing hematopoietic stem cells from pluripotent stem cells.

The present invention provides a method of producing a population of CD34 + hematopoietic precursor cells. Methods of using CD34 + hematopoietic precursor cells for producing natural killer cells (NKs), methods of inducing differentiation of NK cells from pluripotent stem cells (PSCs), and methods of producing terminally differentiated hematopoietic cells from PSCs. Differentiation of immune cells, such as NK cells, from PSC comprises the use of a hematopoietic endothelial induction mixture comprising a WNT signaling pathway activator, a bone morphogenetic protein, and / or a vascular endothelial growth factor. The invention also provides a method for producing hematopoietic stem cells from pluripotent stem cells.