34 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.

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.

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 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.

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.

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 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.

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 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.

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.

This invention provides a method for producing NK cells from undifferentiated stem cells without using feeder cells in serum-free culture medium. [Solution] A method for producing NK cells without using feeder cells, comprising culturing undifferentiated stem cells in a serum-free medium containing BMP4 and a GSK-3 inhibitor to form embryoid bodies, culturing them in a serum-free medium containing VEGF, SCF, and a TGF-β inhibitor, culturing them in a serum-free medium without a TGF-β inhibitor containing VEGF and SCF to differentiate them into hematopoietic progenitor cells, culturing them in a serum-free medium containing IL-7, SCF, Flt-3L, IL-15, and IL-3, culturing them in a serum-free medium without an IL-3 containing IL-7, SCF, Flt-3L, and IL-15 to differentiate them into NK progenitor cells, and culturing them in a serum-free medium containing IL-2, IL-7, SCF, Flt-3L, IL-15, and a serum substitute to differentiate them into mature NK cells.

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.

Disclosed are hematopoietic progenitor kinase 1 (HPK1) degradation / destruction compounds comprising an HPK1 ligand, a degradation / destruction tag, and a linker group, and methods of using such compounds in the treatment of HPK1-mediated diseases.

The invention discloses a 2-amino azacyclo-compound as well as a pharmaceutical composition and application of the 2-amino azacyclo-compound. The structure of the compound is shown as a formula I in the specification. The compound can simultaneously realize tumor immunotherapy and multi-organ protection after cerebral apoplexy by targeted inhibition of activity of hematopoietic progenitor cell kinase 1 (HPK1 / MAP4K1) and phosphorylation of downstream SLP76, and a brand new solution is provided for clinical application of an HPK1 inhibitor.

The present application relates to methods for expanding hematopoietic stem cells (HSC) and / or hematopoietic progenitor cells (HPC) ex vivo and / or in vivo. The methods comprise culturing the HSCs and / or HPCs in the presence of a selective 5-Hydroxytryptamine Receptor 1F (HTR1F) agonist and / or of a Thyroid Hormone Receptor Beta (THRB) agonist, and / or in an air-liquid interface (ALI) culture system. The expanded HSCs and / or HPCs, which maintain engraftment and immune reconstitution properties, may be administered to subjects suffering from various diseases including cancer, immunodeficiencies, myelodysplastic syndrome (MDS) or anemia. The present application also relates to the use of HTR1F and / or THRB agonists for stimulating HSC and / or HPC expansion, and for increasing the number of immune cells or for reconstituting the immune system, in vivo.

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.

A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Compositions and methods for delivering a protein of interest such as a cell homing molecule (e.g., CXCR4) into host cells (e.g., to hematopoietic cells). The compositions and methods provided herein may be used to enhance homing and long-term engraftment of hematopoietic cells post transplantation.

The present invention relates to compounds of formula (I). The compounds may be used to modulate activity of the HPK-1 protein, and thereby treat cancer, viral infection and immune-mediated disorders.

The method for producing human macrophages comprises a culture step of culturing human hematopoietic progenitor cells in a culture medium that does not substantially contain either a macrophage colony stimulating factor or a granulocyte-macrophage colony stimulating factor in the presence of a TREM2 signal activator.

The invention discloses a hematopoietic progenitor cell kinase 1 degradation agent as well as a preparation method and application thereof. The invention relates to a compound shown in a formula (I) or a stereoisomer, a tautomer, a deuterated compound, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or co-crystal of the compound, an intermediate of the compound, and application of the compound in HPK1 kinase related diseases such as cancers.

Compositions and methods are provided relating to FOXP3 gene edited hematopoietic cells, include hematopoietic stem and progenitor cells, lymphoid progenitor cells, and CD4+ T cells. The gene edited cells are useful in cellular therapy to restore normal immune functions and promote immune tolerance. In particular, CD4edFOXP3 T cells, which may be differentiated from FOXP3 gene edited hematopoietic progenitor cells, can physiologically express functional FOXP3 and exert normal immune responses as effector T cells or have immune suppressive characteristics as naturally occurring Treg cells.