57 results about "Hematopoietic progenitor cells" patented technology

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation / disruption compounds including a HPK1 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation / disruption compounds including a HPK1 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

The present disclosure provides methods and compositions for differentiating pluripotent stem cells and derived hematopoietic lineage cells, including hematopoietic endothelial cells, hematopoietic progenitor cells, and natural killer cells. The efficiency of differentiation of hematopoietic endothelial cells, hematopoietic progenitor cells, and natural killer cells can be improved by using the methods and compositions described herein.

Methods and compositions for generating B lineage cells, such as plasmablasts, plasma cells, and protein producing or protein secreting B cells are disclosed. The methods can involve stage-specific differentiation from stem cells or stem cell-derived hematopoietic progenitor cells through one or more intermediates to B lineage cells, such as plasmablasts, plasma cells, and protein producing or protein secreting B cells.

Disclosed are methods and compositions for generating B lineage cells, such as plasmablasts, plasma cells, and protein-producing or protein-secreting B cells. The methods may relate to stage-specific differentiation from stem cells or stem-cell derived hematopoietic progenitors through one or more intermediates to B lineage cells, such as plasmablasts, plasma cells, and protein-producing or protein-secreting B cells.

The invention provides application of SP140 in regulating and controlling differentiation of pluripotent stem cells to hematopoietic stem cells and / or hematopoietic progenitor cells, and relates to the technical field of cell drug preparation. The expression of SP140 in human pluripotent stem cells (hPSC) or in the differentiation process of the human pluripotent stem cells is reduced on the gene level and the protein level, and the human pluripotent stem cells are promoted to be differentiated into human hematopoietic stem cells (HSC) with multiple transplantation potential. The method not only realizes in-vitro regeneration of the hematopoietic stem cells and / or hematopoietic progenitor cells, but also has the characteristics of short differentiation period, high differentiation efficiency and reduction of culture time and cost, and the prepared hematopoietic stem cells express typical biomarkers and have good multi-transplantation chimeric ability. The invention provides a new way for the source of hematopoietic stem cells required by regenerative medicine and treatment of blood and related diseases.

A product comprising: (a) a hematopoietic stem cell (HSC), a hematopoietic progenitor cell (HPC), a myeloid / monocyte-committed progenitor cell, a macrophage or a monocyte comprising a vector, wherein the vector comprises at least one miRNA target sequence operably linked to a transgene, wherein the miRNA target sequence prevents or reduces expression of the transgene in the HSC, HPC and / or myeloid / monocyte-committed progenitor cell, wherein the transgene encodes an orthogonal cytokine; and (b) a T cell or NK cell, wherein the T cell or NK cell expresses an orthogonal receptor.

Provided are DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, that bind to or target a target site in a gene or regulatory element thereof in a stem cell. In some embodiments, the provided DNA-targeting systems promote transcriptional activation of genes that promote lymphoid cell differentiation. In some embodiments, the provided DNA-targeting systems promote differentiation of hematopoietic progenitor cells (HPCs) into a differentiated population of cells. In some embodiments, the differentiated population of cells are lymphoid progenitor cells. In some embodiments, the differentiated population of cells are lymphoid cells. Also provided herein are methods and uses related to the provided compositions, for example in facilitating lymphoid cell differentiation without the provision of extrinsic differentiation signals.

The present invention refers to a novel and efficient method for large-scale selective generation of yδ T cells, preferably human Vδ1+yδ T cells, optimal for clinical application in adoptive immunotherapy of cancer. In this sense, considering that both human cord blood HPCs, currently elected as source of stem cells in the clinic, and human early thymic progenitors can efficiently generate de novo human yδ T cells in response to Notch signalling, and most efficiently in response to the Notch ligand Jag2, the method thus comprises inducing the differentiation of cord blood CD34+ hematopoietic progenitor cells (HPCs) and / or human CD34+ early thymic progenitors, by activating them with Jag2 Notch ligands.

The present disclosure provides a compound of Formula I, a tautomer thereof, a deuterated derivative of the compound or tautomer, a pharmaceutically acceptable salt of the foregoing, a composition comprising a compound of Formula I, a tautomer thereof, a deuterated derivative of the compound or tautomer, and / or a pharmaceutically acceptable salt of the foregoing, # imgabs0 # and methods of using the same to treat diseases, disorders or conditions, e.g., mediated by degradation of protein kinases such as hematopoietic progenitor cell kinase 1 (HPK1, MAP4K1), mitogen-activated protein kinase 1 / 2 (MEK 1 / 2), human Fms-like tyrosine kinase 3 receptor (FLT3) and aurora kinase A

The invention relates to the field of biomedicine, and discloses application of EPTMPA in hematopoietic stem cell in-vitro amplification culture. The invention identifies a brand-new novel small molecule compound EPTMPA capable of remarkably promoting in-vitro expansion and in-vivo transplantation of hematopoietic stem cells and hematopoietic progenitor cells of umbilical cord blood, and the novel small molecule compound EPTMPA can remarkably promote in-vitro expansion of CD34 + hematopoietic stem cells and hematopoietic progenitor cells and maintain the stem property and differentiation potential. EPTMPA is a new discovery and new way for in-vitro amplification of hematopoietic stem cells, but needs more studies to understand the action mechanism, targeting genes and proteins of the hematopoietic stem cells and the regulation effect on self-renewal and differentiation balance of the stem cells. The researches are of great significance to clinical application and product development in the future.

A method of producing macrophages includes a culture step of culturing hematopoietic progenitor cells in the presence of a TREM2 signal activator.

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.

Compositions and methods for treating a blood disorder in a subject comprising delivering a nucleic acid molecule including a nucleotide sequence encoding two to six guide RNAs (gRNAs) into a hematopoietic stem cell (HSC), a hematopoietic progenitor cell (HPC), or a population of hematopoietic stem and progenitor cells (HSPCs) are described.

Compositions and methods of modulating the immune system generally involve immunomodulatory exosomes derived from platelet rich plasma subjected to multiple freeze-thaw cycles and lyophilization. In one or more embodiments, the methods involve administering the composition to a subject in an amount effective to modulate the subject's immune system. In other embodiments, the methods involve culturing a hematopoietic progenitor cell or cell differentiated from a hematopoietic progenitor cell with an immunomodulatory exosome to produce treated cells. The treated cells are then administered to the subject in an amount effective to modulate the subject's immune system.

A hematopoietic stem cell (HSC) proliferation medium includes a basal medium, 0.1 ng / mL to 200.0 ng / mL of thrombopoietin (TPO), 0.1 ng / mL to 200.0 ng / mL of stem cell factor (SCF), 0.1 ng / mL to 20.0 ng / mL of interleukin-3 (IL-3), 0.1 ng / mL to 100.0 ng / mL of interleukin-6 (IL-6), 0.1 ng / mL to 200.0 ng / mL of Flt-3 ligand (FL), 0.1 μg / mL to 20.0 μg / mL of insulin, 0.1 μg / mL to 120.0 μg / mL of transferrin, 0.1 g / L to 3.0 g / L of human serum albumin (HSA), 0.1 μM to 4.0 μM of pyrimido-indole derivative UM729, and 0.1 μM to 2.0 μM of aryl hydrocarbon receptor (AhR) antagonist StemRegenin 1 (SR1). Methods for in vitro proliferation of hematopoietic stem cells (HSCs) and in vitro production of hematopoietic progenitor cells (HPCs) using the HSC proliferation medium are also provided.

The present invention provides methods for producing, from pluripotent stem cells, natural killer (NK) cells or precursor cells thereof. The methods are: a method which is characterized by comprising a) a step for inducing hematopoietic progenitor cells (HPCs) from pluripotent stem cells in vitro, b) a step for amplifying the HPCs in vitro, and c) a step for inducing, from the HPCs, NK cells or precursor cells thereof in vitro, and which is characterized in that a histone methyltransferase and / or an allyl hydrocarbon receptor (AHR) is inhibited in one or more of steps a)-c); and a method which comprises (1) a step for forming, in a first culture medium, pluripotent stem cell spheres having an average particle size of 200 µm or more, (2) a step for inducing a cell population including HPCs through three dimensional culturing of the pluripotent stem cell spheres obtained in step (1) by using a second culture medium containing a histone methyltransferase inhibitor and / or an AHR antagonist, and (3) a step for inducing a cell population including NK cells or precursor cells thereof through three dimensional culturing of the cell population including the HPCs obtained in step (2) by using a third culture medium containing the histone methyltransferase inhibitor and / or the AHR antagonist, and in which one or more of steps (1)-(3) are performed through perfusion culturing, and preferably steps (1)-(3) are performed through continuous perfusion culturing.

The invention provides application of a targeted histone H4K77 acetylation modified substance in preparation of a medicine for delaying immune aging, a modified stem progenitor cell and application of the modified stem progenitor cell, and belongs to the technical field of medicine. The target histone H4K77 acetylation modification or acetylation-like modification substance is a substance for increasing the histone H4K77 acetylation modification level or acetylation-like modification level in hematopoietic stem cells and / or hematopoietic progenitor cells. It is found for the first time that by increasing histone H4K77 acetylation modification or acetylation-like modification, immune senescence and systemic senescence caused by immune senescence can be effectively delayed, and immune senescence and systemic senescence related diseases caused by immune senescence can be treated. The invention provides a new choice for clinically delaying immune senescence and systemic senescence caused by immune senescence and treating immune senescence and systemic senescence related diseases caused by immune senescence, and has a wide application prospect.

The present invention relates to a novel and efficient method for the large-scale selective generation of γδ T cells, preferably human V51+ γδ T cells, optimal for clinical application in adoptive immunotherapy against cancer. In this regard, taking into account that both human cord blood HPCs and human early thymic progenitor cells, the current source of stem cells of choice in the clinic, can efficiently generate de novo human γδ T cells in response to Notch signaling, most efficiently in response to the Notch ligand Jag2, the method comprises inducing the differentiation of cord blood CD34+ hematopoietic progenitor cells (HPCs) and / or human CD34+ early thymic progenitor cells by activating these progenitors with the Jag2 Notch ligand.

Provided are DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, that bind to or target a target site in a DLL4 gene or a VCAM1 gene. In some embodiments, the provided DNA-targeting systems promote transcriptional activation of such genes to promote differentiation of hematopoietic progenitor cells into a differentiated population of cells, such as lymphoid progenitor or lymphoid cells. Also provided herein are methods and uses related to the provided compositions, for example in facilitating lymphoid progenitor cell differentiation.

Heterobifunctional compounds of the formula (I) are provided that are potent degraders or inhibitors of hematopoietic progenitor kinase 1 (HPK1). The compounds are useful to treat or prevent cancer and / or inflammatory and / or autoimmune diseases or symptoms thereof in mammals, particularly humans.

The invention belongs to the technical field of cell biology, and particularly discloses a method for differentiating CXCL13OE stem cells into T cells, which comprises the following steps: (i) culturing iPSC; (ii) carrying out lentivirus transfection to construct a CXCL13 overexpression iPSC; (iii) the CXCL13OE-iPSC differentiates the CXCL13 < + > CD34 < + > hematopoietic progenitor cells; (iv) differentiating the T progenitor cells from the CXCL13 + CD34 + hematopoietic progenitor cells; (v) differentiating the CXCL13 + T progenitor cell into a double positive cell CXCL13 + DP-T cell; and (vi) differentiating a CD8 + CXCL13 + Texp T cell subset by using the double positive CXCL13 + DP-T cells. The CD8 + CXCL13 + Texp T cell subset is further prepared on the basis of constructing CXCL13OE stem cells from the iPSC level, so that on one hand, the problem of low expression of CXCL13 by T cells differentiated by the iPSC is solved, and on the other hand, the difficulty that CXCL13 overexpression and screening cannot be carried out on the CD8 + T cells is solved. Therefore, the complementation of high-targeting and lethality CD8 + T cells lacking in the body of a tumor patient is facilitated.

This method for producing human macrophages includes a culturing step for culturing human hematopoietic progenitor cells in the presence of TREM2 signal activating agent, with a culture medium substantially free of any of a macrophage colony stimulating factor and free of a granulocyte macrophage colony stimulating factor.

The present disclosure provides methods and compositions for differentiating pluripotent stem cells and derived hematopoietic lineage cells, including hematopoietic endothelial cells, hematopoietic progenitor cells, and natural killer cells. The efficiency of differentiation of hematopoietic endothelial cells, hematopoietic progenitor cells, and natural killer cells can be improved by using the methods and compositions described herein.

This invention discloses a traditional Chinese medicine composition for treating neutropenia and / or T-cell cytopenia, its preparation method, and its application. The composition mainly consists of Astragalus membranaceus, Angelica sinensis, ginseng / Codonopsis pilosula, Ganoderma lucidum, Lycium barbarum, and Glycyrrhiza uralensis in a specific ratio. It has a dual effect of increasing neutrophil count and promoting thymic development and T-cell function (enhancing T-cell function). Through multiple pathways, including stimulating hematopoietic progenitor cell proliferation and differentiation, improving the thymic microenvironment, and activating innate and adaptive immunity, it effectively improves the state of reduced immune cells and enhances the body's anti-infection ability.

The invention discloses an amplification culture medium, an amplification method and application of an iPSC (induced pluripotent stem cell) derived hematopoietic progenitor cell population, and relates to the technical field of cell culture. According to the amplification culture medium provided by the invention, animal-derived components are replaced by chemical small molecule combinations, so that the safety of cell products is remarkably improved; the yield of NK cells cultured by the culture medium is greatly increased, the HPC amplification multiple is increased to 2.5 times or more of that of a traditional process by adding tranexamic acid, and the bottleneck of industrial production is broken through. The method provided by the invention improves the process stability. The cells amplified according to the method provided by the invention strengthen the pertinence of lung cancer treatment.

The present invention discloses heterocyclic carboxamide compounds, pharmaceutical compositions, and applications thereof. The heterocyclic carboxamides of the present invention are capable of efficiently and selectively degrading hematopoietic progenitor cell kinase 1 (HPCK1), while lacking degradation activity against other proteins in the same family. Compared to HPCK1 small molecule inhibitors, these heterocyclic carboxamides are more efficient in stimulating T cell anti-tumor immune responses, releasing effector cytokines, and exhibiting stronger anti-tumor activity. #imgabs0#

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation / disruption compounds including a HPK1 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

The present invention provides a method for producing natural killer cells from iPS cells (induced pluripotent stem cells) comprising the steps of: (i) contacting the iPS cells with a composition comprising a GSK-3 inhibitor and a ROCK inhibitor to obtain embryoids, (ii) contacting the embryoids with a composition comprising a TGF [beta] receptor inhibitor to obtain hematopoietic progenitor cells, (iii) culturing the hematopoietic progenitor cells to obtain lymphocyte progenitor cells, and (iv) differentiating and expanding the lymphocyte progenitor cells into natural killer cells.

Provided herein are methods for expanding populations of hematopoietic stem cells (HSCs) or hematopoietic progenitor cells (HPCs) using extracellular vesicles isolated from hematopoietic stem cells (HSC-derived EVs) or from HPCs (HPC-derived EVs). Also provided are methods of using the isolated HSC-derived EVs and / or HPC-derived EVs as well as the HSCs and HPCs generated by or exposed to the methods disclosed herein.