56 results about "Hematopoietic cell" patented technology

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 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 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.

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 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.

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.

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 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.

The application relates to the field of biological medicine, in particular to application of lysosome ion channel CLN7 as a target in preparation of a drug for treating myeloid leukemia. In K562 and other myeloid leukemia cell strains, the proliferation ability of leukemia cells is significantly inhibited after CLN7 expression is knocked down by using specific shRNA interference technology, and cell apoptosis is greatly promoted. Experiments prove that inhibition of CLN7 enhances lysosome degradation function, promotes degradation of leukemia-related pathogenic proteins, and blocks survival signal dependence of leukemia cells. Preliminary results show that the influence of inhibition of CLN7 on normal hematopoietic cells is significantly lower than that on leukemia cells, which indicates that the treatment window is good.

Provided herein are systems of modulating gene expression, methods of use thereof, and cells engineered thereof for the purpose of differentiating cells, for example hematopoietic cells.

The present invention relates to methods and compositions for inducing differentiation of hematopoietic cells. The present invention provides culture platforms, cell culture media, and methods for differentiating pluripotent cells into hematopoietic cells. The present invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein that allow for feeder cell-free monolayer culture without EB formation. In particular, the pluripotent stem cell-derived hematopoietic cells of the present invention include, and are not limited to, iHSCs, permanent hemogenic endothelial cells, hematopoietic multipotent progenitor cells, T cell progenitor cells, NK cell progenitor cells, T cells, NK cells, NKT cells, and B cells.

Provided are methods and medicaments for treating endometriosis in an individual in need thereof, the methods comprising administering to the individual an effective amount of a hematopoietic cell kinase inhibitor.

The invention relates to dosing regimens for antibody drug conjugates, as well as methods of administering said dosing regimens to patients suffering from or at risk of various diseases and conditions such as autoimmune diseases, cancers, and Graft versus Host Disease (GvHD), among others, by administration of an antibody drug conjugate (ADC), capable of binding an antigen expressed by a hematopoietic cell, such as a hematopoietic stem cell, an immune cell or a cancer cell.

A method for generating definitive hematopoietic cells from source cells comprising at least one of differentiating iPS cells, cells directly reprogrammed into hematopoietic precursors, cells directly reprogrammed into definitive hematopoietic cells, and adult or neonatal hematopoietic cells from bone marrow, umbilical cord blood, placenta, or mobilized peripheral blood, comprising activating the tricarboxylic acid cycle of the source cells using a metabolic regulator. Another method relates to generating primitive hematopoietic cells from source cells comprising at least one of differentiating iPS cells, cells directly reprogrammed into hematopoietic precursors, cells directly reprogrammed into definitive hematopoietic cells, and adult or neonatal hematopoietic cells from bone marrow, umbilical cord blood, placenta, or mobilized peripheral blood, comprising inhibiting the tricarboxylic acid cycle of the source cells using a metabolic regulator. Some embodiments relate to metabolic regulators for activation of the tricarboxylic acid cycle of source cells for the production of definitive or primitive hematopoietic cells.

A method of use of a synthetic SCGB, and compositions thereof, to prevent the development or reduce the development of antibodies against a foreign antigen or set of antigens in the subject that receives the antigen(s) is provided. A synthetic SCGB being recombinant human CC10 protein is provided. The foreign antigen(s) is / are a cell, tissue or organ from a donor subject is administered, introduced, or transplanted into a recipient subject, a lung transplant, transplanted kidney, heart, liver, hematopoietic cell, or any other tissue or organ, antigen(s) is / are from human or non-human origin, purified therapeutic proteins or other drugs, food or drink, self-antigen or an allergen.

The present disclosure provides low immunogenicity engineered cells, including induced pluripotent stem cells (iPSCs), hematopoietic cells and primary cells derived therefrom, pharmaceutical compositions comprising the cells, and methods of use thereof, where the cells are transfected with one or more genes to reduce activation of allogeneic immune cells.

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.