29 results about "Hematopoietic progenitor" patented technology

A method is provided for recruiting hematopoietic progenitor cells from the bone marrow of a target to the peripheral blood. The method comprises (a) administering an effective dose of natalizumab to the target, and (b) administering an effective dose of a CXCR4 inhibitor to the target, at least 48 hours after step (a). The use of such recruitment procedures in cell collection and therapy is also provided.

The identification of differentiation stages, differentiation trajectories, and expression profiles of hematopoietic progenitor cells and fate-determining factors, and the application thereof are provided. The enrichment and identification of rare hematopoietic progenitor cells, as well as the identification of and their fate-determining genes, are also provided. A method for reconstructing hematopoietic hierarchy is provided, which includes fate-determining factors, differentiation trajectories, and patterns within lineage commitment processes.

The present disclosure provides methods for generating hematopoietic progenitor cells. In some embodiments, the methods involve an in vitro or ex vivo cell culture model utilizing rentionic acid signaling for producing hematopoietic progenitor cells from pluripotent stem cells.

The present invention relates to processes for the in vitro production of hematopoietic cells, comprising contacting hematopoietic progenitors with a DNTM3A inhibitor, hematopoietic cells comprising said DNTM3A inhibitor and uses thereof.

Disclosed herein are compounds that are Hematopoietic Progenitor Kinase 1 (HPK1) inhibitors having a structure according to Formula I, and compositions containing those compounds. Methods of preparing the compounds, and methods of using the compounds for the treatment of diseases, disorders, or conditions are also described.

The invention provides a smoke disease model and a construction method and application thereof, and belongs to the technical field of smoke disease model construction. The method for constructing the smog disease model comprises the following steps: extracting CD34 + hematopoietic progenitor cells in peripheral blood of a smog disease patient, reprogramming to generate hiPSC, further differentiating into brain organs and vascular organs, fusing the brain organs and the vascular organs, and culturing and constructing the vascularized brain organ smog disease model. The smoke disease model constructed by adopting the construction method disclosed by the invention can simulate and reproduce phenotypes such as tiny branch increase, macrovascularization, pericytopenia, smooth muscle fibrosis deposition, abnormal angiogenesis increase and the like in clinical core pathological phenotypes of smoke disease patients, and is superior to existing animal and cell models to a certain extent.

The present invention provides a method for producing a natural killer cell from an iPS (Induced pluripotent stem) cell, comprising steps of: (i) contacting an iPS cell with a composition comprising a GSK-3 inhibitor and a ROCK inhibitor to obtain an embryoid body, (ii) contacting the embryoid body with a composition comprising a TGFβ receptor inhibitor to obtain a hematopoietic progenitor cell, (iii) culturing the hematopoietic progenitor cell to obtain a lymphocyte progenitor cell, and (iv) differentiating and expanding the lymphocyte progenitor cells to a natural killer cell.

This invention discloses a method for co-culturing and inducing stem cell differentiation into hematopoietic progenitor cells. The method includes the following steps: culturing pluripotent stem cells to obtain embryoid bodies; culturing the embryoid bodies for mesodermal differentiation to obtain mesodermal cells; culturing the mesodermal cells for hematopoietic endothelial differentiation to obtain hematopoietic endothelial cells; and co-culturing the hematopoietic endothelial cells with mesenchymal stem cells to obtain hematopoietic progenitor cells. Through optimization of the culture system, the differentiation efficiency and the number of hematopoietic progenitor cells obtained are significantly improved; by co-culturing mesenchymal stem cells with hematopoietic endothelial cells, the number of hematopoietic progenitor cells is further increased while maintaining high differentiation efficiency and uniform and stable expression of various markers.

The present disclosure relates to a method for induced differentiation of stem cells into hematopoietic progenitor cells. The method comprises the following steps: culturing pluripotent stem cells to obtain an embryoid body; performing mesoderm differentiation culture on the embryoid body to obtain mesoderm cells; performing hemogenic endothelium differentiation culture on the mesoderm cells to obtain hemogenic endothelial cells; and performing hematopoietic progenitor cell differentiation culture on the hemogenic endothelial cells to obtain hematopoietic progenitor cells. According to the present disclosure, the hematopoietic progenitor cells can be rapidly and efficiently prepared, and the prepared hematopoietic progenitor cells have an ability to stably differentiate into a plurality of different blood cells (including simultaneously having erythroid, myeloid, and lymphoid cells); by optimizing a culture system, the differentiation efficiency is significantly improved and the number of hematopoietic progenitor cells obtained is significantly increased.

The present disclosure provides methods for making bone marrow hematopoietic progenitors lacking NF-κB p50 protein subunit (p50) and STAT6, or bone marrow hematopoietic progenitors lacking NF-κB p50 protein subunit and NF-κB p52 protein subunit. The progenitor cells are expanded, exposed to a myeloid cytokine, and provided intravenously to treat various malignancies. The infused cells have the potential to generate mature granulocytes, monocytes, macrophages, and dendritic cells. Methods for the genetically manipulation of a subject's hematopoietic progenitors during the expansion phase to reduce or eliminate expression of p50, p52, and / or STAT6 are also contemplated, and these progenitor cells may be combined with other therapeutic agents to maximize efficacy.

The invention provides methods for generating human CD34+, CD43+, and CD90+ hematopoietic progenitor cells from hematopoietic stem cells. The methods include the use of chemically-defined culture media. Isolated cell populations are also provided.

The invention provides methods for generating human CD34+, CD43+, and CD90+ hematopoietic progenitor cells from hematopoietic stem cells. The methods include the use of chemically-defined culture media. Isolated cell populations are also provided.

The method of generating multipotent stem cells is a method for producing and / or expanding multipotent stem cells by delivering at least one reprogramming protein into somatic cells. The at least one reprogramming protein includes a Master Regulator (MR) protein, which may be BAZ2B, ZBTB20, ZMAT1, CNOT8, KLF12, DMTF1, HBP1, or FLI1. The bromodomain protein BAZ2B, in particular, was identified by first generating bi-species heterokaryons by fusing Tcf7l1− / − murine embryonic stem cells (ESCs) with human B-cell lymphocytes. Reprogramming of the B-cell nuclei to a multipotent state was tracked by human mRNA transcript profiling at multiple timepoints. Interrogation of a human B-cell regulatory network with gene expression signatures collected from such reprogramming time series identified eight candidate Master Regulator proteins, which were validated in human cord blood-derived hematopoietic progenitor and lineage-committed cells.

The present invention relates to methods for deriving human hematopoietic progenitors, primitive macrophages, and microglial cells from human pluripotent stem cells. In particular, provided herein are highly efficient and reproducible methods of obtaining human primitive macrophages and microglia from human pluripotent stem cells, where the primitive macrophages and microglia can be suitable for clinically relevant therapeutic applications.

The present invention relates to methods for deriving human hematopoietic progenitors, primitive macrophages, and microglial cells from human pluripotent stem cells. In particular, provided herein are highly efficient and reproducible methods of obtaining human primitive macrophages and microglia from human pluripotent stem cells, where the primitive macrophages and microglia can be suitable for clinically relevant therapeutic applications.

Provided are compounds of Formula (I), a tautomer thereof, a deuterated derivative of the compound or the tautomer, and a pharmaceutically acceptable salt of the foregoing, compositions comprising the compounds of Formula (I), a tautomer thereof, a deuterated derivative of the compound or the tautomer, and / or a pharmaceutically acceptable salt of the foregoing, and methods of using the same, in treating, for example, the diseases, disorders, or conditions mediated by the degradation of protein kinases, such as Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), Mitogen-activated protein kinases 1 / 2 (MEK 1 / 2), Human Fms-like tyrosine kinase 3 receptor (FLT3), and Aurora kinases.

Provided is a method for producing hematopoietic progenitor cells with which it is possible to stably obtain hematopoietic progenitor cells from pluripotent stem cells and with which it is possible to improve the efficiency of inducing differentiation from pluripotent stem cells into hematopoietic progenitor cells. This method for producing hematopoietic progenitor cells is provided with: a cell mass formation step in which pluripotent stem cells are cultured using a cell culture substrate provided with a substrate and a cell scaffold material arranged in a dot shape on a first surface of the substrate, and cell mass is formed on the surface of the cell scaffold material; and a differentiation induction step for inducing the differentiation of the obtained cell mass into a cell population containing hematopoietic progenitor cells.

The present disclosure relates generally to certain 6-azabenzimidazole compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions disclosed herein may be used for the treatment or prevention of diseases, disorders, or infections modifiable by hematopoietic progenitor kinase 1 (HPK1) inhibitors, such as HBV, HIV, cancer, and / or a hyper-proliferative disease.

The application discloses an isofuranone compound, a medicine combination and use thereof, and the isofuranone compound disclosed by the application can efficiently and selectively degrade hematopoietic progenitor kinase 1 protein, and has no degradation activity on other proteins in the same family. Compared with a small molecule inhibitor of hematopoietic progenitor kinase 1, the isofuranone compound can more efficiently stimulate T cell anti-tumor immune response, release effector cytokines, and has stronger anti-tumor activity.

The present application provides a method for producing megakaryocytes, which comprises a step of forcibly expressing an oncogene, a homologous frame gene, and an apoptosis-inhibiting gene in a hematopoietic progenitor cell and culturing the cell. The present application also provides a kit for manufacturing megakaryocytes, mature megakaryocytes, or platelets, comprising a vector comprising an oncogene, a homologous frame gene, and an apoptosis suppressor gene.

Provided are xenogenic-free methods and compositions for generating hematopoietic progenitors and natural killer (NK) cells in 3D suspension culture.

The present invention provides a method for producing natural killer (NK) cells or precursor cells thereof from pluripotent stem cells, comprising a) a step of in vitro inducing hematopoietic progenitor cells (HPC) from pluripotent stem cells, b) a step of in vitro expanding HPC, and c) a step of in vitro inducing NK cells or precursor cells thereof from HPC and inhibiting histone methyltransferase and / or aromatic hydrocarbon receptors (AHR) in one or more of steps a) to c); and a method comprising (1) a step for forming pluripotent stem cell spheres having an average particle diameter of 200 [mu] m or more in a first culture medium, (2) a step for inducing the pluripotent stem cell spheres obtained in step (1) into a cell population containing HPC by three-dimensional culture using a second culture medium containing a histone methyltransferase inhibitor and / or an AHR antagonist, and (3) a step for inducing the pluripotent stem cell spheres obtained in step (2) into a cell population containing HPC. And (3) a step in which the cell population containing HPC obtained in step (2) is induced into a cell population containing NK cells or precursor cells thereof by three-dimensional culture using a third culture medium containing a histone methyltransferase inhibitor and / or an AHR antagonist, and one or more of steps (1) to (3) are performed by a perfusion culture method. Steps (1) to (3) are preferably performed by a continuous perfusion culture method.

Induced pluripotent stem cells (iPSCs) and iPSC-derived natural killer (iNK) cells co-expressing interleukin-15 (IL-15) and a chimeric antigen receptor (CAR) targeted to mesothelin are described. Nucleic acid molecules and vectors encoding a mesothelin-targeted CAR and IL-15, such as for transduction of iPSC and iNK cells, are also described. The CAR / IL-15-expressing iNK cells can be used for the treatment of solid tumors, such as mesothelin-positive solid tumors. Methods of producing hematopoietic progenitor cells and iNK cells from an iPSC line, such as the LiPSC-GR1.1 line, are also described.

Methods are provided to manipulate phagocytosis of cells, including hematopoietic cells, e.g. circulating hematopoietic cells, bone marrow cells, acute leukemia cells, etc.; and solid tumor cells. In some embodiments of the invention the circulating cells are hematopoietic stem cells, or hematopoietic progenitor cells, particularly in a transplantation context, where protection from phagocytosis is desirable. In other embodiments the circulating cells are leukemia cells, particularly acute myeloid leukemia (AML), where increased phagocytosis is desirable.

The invention discloses a pyrazinecarboxamide compound as well as a pharmaceutical composition and application of the pyrazinecarboxamide compound. The pyrazinecarboxamide compound (formula I) provided by the invention can efficiently and highly selectively degrade hematopoietic progenitor cell kinase 1, and has no degradation activity on other proteins of the same family. Compared with a hematopoietic progenitor cell kinase 1 small molecule inhibitor, the hematopoietic progenitor cell kinase 1 small molecule inhibitor can more efficiently stimulate T cell anti-tumor immune response and release effector cell factors, and has higher anti-tumor activity.