121 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 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.

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 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 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.

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.

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.

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.

The present disclosure relates to an engineered hematopoietic cell comprising a very late antigen-4 (VLA-4) variant and uses thereof in treating an inherited genetic disorder or an acquired disorder.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

The present invention relates to regulatory T cell and uses thereof. By their immunosuppressive and anti-inflammatory activities, regulatory T cells play a central role in peripheral tolerance and thus critically prevent the development of autoimmune and inflammatory disorders. The inventors showed that Foxp3+CD4+ Tregs express high levels of LTα, which negatively regulates their immunosuppressive signature. They demonstrated that the adoptive transfer of LTα− / − Tregs in mice protects from dextran sodium sulfate (DSS)-induced colitis and attenuates inflammatory bowel disease (IBD), multi-organ autoimmunity and the development of CAC. The inventors also showed that by mixed bone marrow chimeras that LTα expression specifically in hematopoietic cells negatively controls the immunosuppressive signature of Tregs. In particular, the present invention relates to regulatory T cell characterized in that it does not express or expresses reduced levels of lymphotoxin alpha.

The present disclosure provides a clinically applicable method to re-balance production of hematopoietic cells in a mammal, including without limitation an aged mammal, by disrupting the CCL5-CCR5 axis.

Compositions and methods are provided for the culture of functional bone marrow, allowing analysis of the responsiveness to therapeutic agents, and for studying the interactions of cells in the bone marrow niche.

The present disclosure includes adenoviral vectors characterized by efficient transduction of hematopoietic cells (e.g., one or more particular types of hematopoietic cells), e.g., for in vivo or ex vivo gene therapy. The present disclosure includes, among other things, Ad3, Ad5, Ad7, Ad11, Ad14, Ad16, Ad21, Ad34, Ad35, Ad37, and Ad50 vectors and genomes. Ad3, Ad5, Ad7, Ad11, Ad14, Ad16, Ad21, Ad34, Ad35, Ad37, and Ad50 vectors and genomes of the present disclosure can include therapeutic payloads.

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 relates generally to methods and compositions for providing multi-lineage hematopoietic precursor cells from pluripotent stem cells (PSCs). The PSCs comprise expression constructs encoding ETS / ERG gene, GATA2, and HOXA9. Methods for providing hematopoietic stem cells capable of long-term engraftment in a mammal (e.g., human) are also provided. Further provided are therapeutic compositions, including the provided hematopoietic stem cells and precursors of hematopoietic cells, and methods of using them to treat subjects.

The present invention provides a culture medium for amplifying hematopoietic cells having cell division ability, the culture medium containing a compound (I) represented by formula (1) or a physiologically acceptable salt thereof: in the formula (1), R1, R2, and R3 are each independently any one of hydrogen, a linear or branched C1-C4 alkyl group, bromine, and iodine, R4 is any one of a linear or branched C1-C4 alkyl group, bromine, and iodine, and R1, R2, and R3 are each independently any one of hydrogen, linear or branched C1-C4 alkyl groups, bromine, and iodine. R5 is any one of oxygen, methylene and a chemical bond, R6 is hydrogen or-NH2, R7 is hydrogen or-COOH, and R6 and R7 are not hydrogen at the same time.

The present disclosure provides nucleic acid constructs engineered to express therapeutic expression products from regulatory sequences that drive expression in hematopoietic cell populations. For example, the present disclosure includes nucleic acid constructs in which a first regulatory sequence drives expression of a first therapeutic expression product and a second regulatory sequence drives expression of a second therapeutic expression product. Nucleic acid constructs can be delivered to cells or subjects by viral vectors, including adenoviral vectors, e.g., for the treatment of cancer.