86 results about "Hematopoietic cell" patented technology

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 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 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 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 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 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.

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.

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.

Provided are engineered cells, including induced pluripotent stem cells (iPSCs), primary immune cell, and hematopoietic cells derived therefrom, pharmaceutical compositions comprising said cells, and methods of use of same, wherein one or more genes are disrupted and / or transfected into said cells, such that ADCC activation exhibits an improved safety profile.

The invention provides culture platforms, cell media, and methods of differentiating pluripotent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, NK cells, NKT cells and B cells.

Methods to improve homing and engraftment of hematopoietic stem cells, particularly cord blood CD34+ cells, for use in hematopoietic cell transplantation through the regulation of expression of YTHDF2 or FTO in CD34+ cells. The methods include transiently repressing expression of YTHDF2 through exposure of the CD34+ cells to YTHDF2 repressor compound. The methods also include exposing CD34+ cells to a FTO expression activator compound to transiently increase FTO expression in the cells.

The application discloses application of bone marrow vascular endothelial cells in myelodysplastic syndrome (MDS). The application provides application of bone marrow vascular endothelial cells as a marker in any one of the following: preparation of a product for detecting or assisting in detecting the disease progression of MDS, preparation of a product for diagnosing or assisting in diagnosing MDS, and preparation of a product for distinguishing or assisting in distinguishing MDS and non-MDS. Researches of the application find that the number of bone marrow vascular endothelial cells gradually increases from MDS-MLD, MDS-EB to AML patients, but the abnormal function gradually aggravates. In addition, with the disease progression, the supporting ability of bone marrow vascular endothelial cells of MDS patients to normal hematopoietic cells in vitro decreases, and the supporting ability to malignant hematopoietic cells increases. The application has important significance for detecting the occurrence and development of MDS, especially for monitoring the disease progression of MDS.

As demonstrated herein, a preferential and progressive expansion of a subset of hematopoietic cells bearing somatic mutations in one or more HSC cardiometabolic driver genes leads to pro-inflammatory signaling at multiple levels. Accordingly, provided herein are compositions, methods, and assays for modulating a HSC cardiometabolic driver gene mutation-mediated proinflammatory activity.

Methods, polynucleotides, and compositions for generating engineered Treg cells are provided. The methods, polynucleotides, and compositions enable the reprogramming of hematopoietic cells into Treg cells by constitutive or controlled expression of FOXP3 in engineered cells, so that engineered Treg cells can suppress the activation and proliferation of responder T cells.

The present disclosure provides hematopoietic cells in which one or more selected second signal molecules are knocked out such that stimulation of the hematopoietic cells to heterologous CD8 + T cells is significantly reduced.

To provide a cryopreservation liquid for hematopoietic cells with a high cell survival rate, and a cryopreservation method for hematopoietic cells.SOLUTION: A cryopreservation liquid for hematopoietic cells includes, in a solvent: a polymer having a viscosity average molecular weight of more than 3000 and 500000 or less, the polymer including a monomer having a hydrophilic group as a repeat unit, or a salt thereof; a saccharide having a viscosity average molecular weight of 3000 or less, or a salt thereof; and a polyhydric alcohol. There is also provided a cryopreservation method for hematopoietic cells using the cryopreservation liquid.SELECTED DRAWING: None

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 discloses an sgRNA, the nucleotide sequence of which is shown in one of SEQ ID Nos. 1-21. The sgRNA provided herein can efficiently knock out or down the human HLA-A gene, and nearly completely covers the HLA-A genotype of the Chinese population. The sgRNA provided herein has high targeting, and after knocking out or down the HLA-A gene in human hematopoietic cells, it has no significant effect on the expression of HLA-B, HLA-C, and HLA-II class molecules. It also has low cytotoxicity, exhibits significant advantages in gene therapy, and has great clinical application prospects in the field of cell therapy.

Compounds which are oxadiazaborole derivatives are disclosed, including compounds of the following genus:The compounds are inhibitors of hematopoietic cell kinase (HCK) and exhibit anti-fibrotic and anti-proliferative effects. They are useful in the treatment of a variety of disorders, including a fibrosis or a fibrotic disease, such as renal fibrosis.