27 results about "Blood-forming stem cell" patented technology

The invention discloses a culture medium composition for inducing human pluripotent stem cells to differentiate into human iAGM hematopoietic organoid, human embryonic stem cells are differentiated into the human iAGM hematopoietic organoid through combination and matching of different cell factors in stages, and the generated hematopoietic stem cells have high primitiveness and authenticity, so that the functionality of the hematopoietic stem cells is finally guaranteed.

We have discovered that allogeneic HSC-engineered human iNKT (3rdHSC-iNKT) cells display potent anti-GvHD functions, by eliminating antigen-presenting myeloid cells in vitro and in xenograft models, without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia. The 3rdHSC-iNKT cells closely resembled the CD4−CD8− / + subsets of endogenous human iNKT cells in phenotype and functionality. Embodiments of the invention harness these discoveries in new methods and materials for alleviating graft versus host disease.

Disclosed herein are devices, compositions, methods, and systems for identifying mammalian cells, especially erythrocytes, with enhanced characteristics, such as hemolysis, stress tolerance, oxygen capacity, and energy metabolism. In some embodiments, the devices, compositions, methods, and systems may be useful in identifying a subject for donating erythrocytes, with enhanced stress resistance, with enhanced physical performance such as oxygen consumption, and strenuous or prolonged physical activities, hemorrhage, or resistance to high altitude hypoxia. Subjects may also be identified for donating cells for use in manufacture of next-generation ex vivo farmed RBCs with optimal storage and resuscitation performances. The disclosed devices, compositions, methods and systems are also useful in the bioengineering of red blood cells and red blood cell precursor ex vivo from hematopoietic stem cells or induced pluripotent stem cells, as well as ithe prediction of cancer progression, severity and responses to therapies targeting glycolysis.

A method for preparing hematopoietic stem cells and progenitor cells is provided for producing hematopoietic stem / progenitor cells (HSPCs) from embryonic stem cells or iPSCs. Also provided are a hematopoietic stem / progenitor cell (HSPC) culture product generated by the method, and the use of differentiating the hematopoietic stem / progenitor cells (HSPCs) into blood cells of interest. The method successfully achieves efficient differentiation into HSPCs, and the obtained culture product does not contain heterologous substances, meets the GMP standard, and is prone to large-scale production. Additionally, the method also has the advantages of shorter differentiation time and higher efficiency.

The present invention relates to methods of using base editors for the efficient genetic engineering of cells, particularly primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the present invention is directed to rules for designing highly active and specific TALE base editors that exhibit an improved on-target / off-target activity ratio, useful for producing therapeutic-grade complex gene-edited cells or for performing in vivo gene therapy. The resulting TALE base editors can be used alone or in combination with rare-cut endonucleases in various gene therapy approaches.

The present invention belongs to the technical field of medical equipment, and specifically is a medical hematopoietic stem cell collector, comprising a blood collection needle and a blood collection needle tube; a liquid outlet is provided at the bottom of the blood collection needle tube; a negative pressure mechanism is connected to the inner sliding seal of the blood collection needle tube; a baffle located on the left side of the negative pressure mechanism is installed on the inner wall of the blood collection needle tube; a sleeve is sleeved on the outer wall of the blood collection needle tube, a through hole is provided on the top of the sleeve, and the sleeve can rotate with the blood collection needle tube as the axis; a liquid tank is fixedly installed on the right side of the blood collection needle, and the blood collection needle and the liquid tank are connected; the push plate is driven to move vertically downward by the lifting mechanism, and the heparin liquid on the top of the push plate will also move downward, thereby reducing the squeezing of the negative pressure mechanism by the heparin liquid, and the negative pressure mechanism moves to the right side in the blood collection needle tube, so that the negative pressure inside the blood collection needle tube draws blood into the blood collection needle tube through the blood collection needle, thereby achieving the effect of controlling the total amount of blood collected.

The invention relates to a construction method of a peripheral red blood cell humanized mouse, which comprises the following steps: transplanting human hematopoietic stem cells into the mouse and then applying a red blood cell inducer to the mouse, or applying a red blood cell inducer to the mouse and then infusing human red blood cells into the mouse. The red blood cell inducer comprises an antibody targeting mouse macrophage, dexamethasone or a derivative thereof, and a human macrophage colony stimulating factor. In a mouse transplanted with human hematopoietic stem cells, one or more of an antibody targeting mouse macrophages, dexamethasone and a human macrophage colony stimulating factor can be used in the red blood cell induced maturation process, and high-level human red blood cell reconstruction can be quickly realized within three weeks; the maturity and the denucleation ratio of peripheral human erythrocytes reconstructed in the mouse are completely consistent with those of normal human blood; in a mouse transplanted with human erythrocytes, the erythrocyte induction process can be single treatment of an antibody or dexamethasone, or combined use of the antibody and dexamethasone. The invention also provides application of the peripheral erythrocyte humanized mouse.

Disclosed in the present invention is a method for counting CD34-positive cells in hematopoietic stem cells, which method is characterized by comprising the following steps: extracting hematopoietic stem cells, adding a red blood cell lysis buffer for lysis, centrifuging and washing same, and resuspending same to obtain a cell suspension; putting the cell suspension into a flow tube, adding a CD34 antibody and a CD45 antibody, uniformly mixing same, then adding a fluorescent nucleic acid dye, centrifuging and washing same, and then counting the CD34-positive cells by means of a flow cytometer. In the method for counting CD34-positive cells in hematopoietic stem cells of the present invention, the extracted hematopoietic stem cells are subjected to red blood cell lysis removal and then nucleic acid dyeing, and are prepared into a cell suspension, so that the interference of impurities such as red blood cells can be reduced, and the accuracy of flow cytometry counting is improved. The method has the advantages of simple operation, easy operation, and strong consistency in repeated operations. Furthermore, the provided CD34-positive-cell counting gating method has strong universality, and effectively screens out CD34-positive cells for counting.

The utility model relates to the technical field of umbilical cord blood separation, and particularly discloses an umbilical cord blood separation preparation bag which comprises a plurality of blood bags, a main pipeline, a three-way valve, a needle head and a Luer taper. Wherein each blood bag is used for storing umbilical cord blood in the blood collection bag; one end of the main pipeline is communicated with the plurality of blood bags; an outlet of the three-way valve communicates with the main pipeline; the needle is communicated with one inlet of the three-way valve; the Luer taper is communicated with the other inlet of the three-way valve; the Luer taper is used for being connected with an injector so that the injector can be communicated with the blood bag. By means of the arrangement, when the needle head is communicated with the blood collection bag, transfer of umbilical cord blood from the blood collection bag to the blood bag can be completed; when the Luer taper is communicated with the injector, the reagent in the injector can be smoothly injected into the blood bag, leakage is avoided, and the safety of reagent adding is improved. Wherein the reagent is a hematopoietic stem cell separating medium.

The invention relates to a cell preparation technology in biomedical engineering, and particularly discloses a preparation method of umbilical cord blood hematopoietic stem cells. According to the method, an umbilical cord blood sample is transferred to a blood collection bag system which is in sterile connection, erythrocyte sedimentation is promoted through inverted centrifugation, an erythrocyte layer is removed through a constant-speed plasma separation technology, separation of plasma and target cell components is achieved through upright centrifugation, and finally the high-purity hematopoietic stem cell product is obtained. The whole preparation process is completed under the condition that no sedimentation reagent is added in the whole process, and cell activity and functional integrity are kept in a low-temperature environment in the whole process through the combined action of specific centrifugal force and proper duration in cooperation with layered control operation. According to the pure physical separation system established in the invention, clinical potential safety hazards caused by exogenous additives are effectively eliminated, synchronous improvement of cell recovery efficiency and product safety is realized through optimized process parameters and operation specifications, and a more reliable cell preparation solution is provided for clinical application.

The invention relates to the technical field of cell cryopreservation, in particular to full-automatic hematopoietic stem cell cryopreservation liquid preparing and subpackaging equipment which comprises a bearing box, and a raw material preparation area, a preparing area and a subpackaging area are arranged in the bearing box; a shaking table oscillator is installed in the preparation area, an infusion assembly is further arranged in the preparation area, the bottom of the infusion assembly is communicated with a cryopreservation pipe, and the cryopreservation pipe is communicated with a cryopreservation bag integrally formed with the cryopreservation pipe; a bag hanging plate is arranged in the subpackaging area, a hanging groove is formed in the bag hanging plate, symmetrical sliding grooves are formed in the inner side wall of the hanging groove, clamping blocks are slidably connected into the sliding grooves, a first heat sealing assembly and a second heat sealing assembly are arranged at the bottom of the inner side wall of each clamping block, and a third heat sealing assembly is arranged at the communicating position of the infusion assembly and the cryopreservation pipe. According to the invention, cryopreservation liquid preparation, cryopreservation liquid subpackaging and heat sealing of cryopreservation bags and cryopreservation tubes are integrated, and the technical defects of tedious manual operation, high cross contamination risk and large loss of precious stem cells are overcome by adopting pipeline pressure monitoring and multi-node synchronous heat sealing technologies.

The present invention relates to a method for producing red blood cells, and more specifically, to (S1) culturing pluripotent stem cells to obtain a culture medium containing hematopoietic stem cells, and (S2) obtaining CD41 from the culture medium. - and CD34 - The present invention relates to a method for producing red blood cells of superior quality in a short period of time, comprising the steps of (S3) obtaining a cell population and (S3) maturing the obtained cell population in a first medium containing erythropoietin.

This invention relates to the diagnosis and evaluation of juvenile myelomonocytic leukemia (JMML). In particular, the invention relates to a method for diagnosing JMML in a subject, comprising: a) at least one biomarker present on or in hematopoietic stem cells and progenitor cells (HSPCs) in a biological sample, i) CD52, RAMP1, LTB, LST1, JAML, IFITM3, CD7, CD69, CD164, CD74, TNF, TFPI, DLK1, CD82, IGHM, CALCRL, RALA, SLC2A5, HSPA5, HLA-DRA, RAB11A, SELL, VAMP5, FCMR, CLEC7A, NDFIP The present invention relates to a method comprising the steps of: 1) determining the amount of at least one biomarker selected from each of the following groups: 1) Group I consisting of CLEC9A, HCST, LPAR6, HLA-DQA1, HLA-DRB5, and CD34; and 2) Group II consisting of IGLL1, BEST1, EREG, SLC5A3, SERK, PRRG3, NINJ1, MGST1, and HLA-G; b) comparing the determined amount in step a) with a reference; and c) diagnosing JMML based on the comparison in step b). Furthermore, the present invention relates to a method for classifying subjects suffering from JMML into a low- or high-risk JMML group. Furthermore, the present invention relates to the use of at least one biomarker present on or in HSPC in a biological sample for diagnosing JMML to a low- or high-risk JMML group in subjects who have JMML or are at risk of developing it. Furthermore, the present invention relates to a kit for diagnosing JMML in a subject or for classifying a subject suffering from JMML into a low- or high-risk JMML group.Furthermore, the present invention relates to an inhibitor for use in the treatment and / or prevention of JMML that specifically inhibits at least one biomarker selected from the group consisting of CD52, RAMP1, LTB, LST1, JAML, IFITM3, CD7, CD69, CD164, CD74, TNF, TFPI, DLK1, CD82, IGHM, CALCRL, RALA, SLC2A5, HSPA5, HLA-DRA, RAB11A, SELL, VAMP5, FCMR, CLEC7A, NDFIP1, CLEC9A, HCST, LPAR6, HLA-DQA1, HLA-DRB5, CD34, IGLL1, BEST1, EREG, SLC5A3, SELK, PRRG3, NINJ1, MGST1, and HLA-G, which are present on or in hematopoietic stem cells and progenitor cells (HSPCs). The present invention further relates to a pharmaceutical composition for use in the treatment and / or prevention of JMML, comprising at least two inhibitors according to the present invention. Finally, the present invention envisions a method for treating and / or preventing JMML.

In various aspects and embodiments, the disclosure provides cell populations, or "banks" of cells thereof (e.g., cell collections), to provide immunocompatible, allogeneic cell therapies covering global, ethnical, and disease-specific populations. In various aspects and embodiments, the cell banks and progeny thereof maintain sufficient HLA class I and HLA class II functions while promoting patient mating to prevent or reduce graft versus host disease (GVHD) or graft rejection. The disclosure further provides methods for creating a cell bank by gene editing, and methods for cell therapies involving cells or tissues derived from a cell bank, including but not limited to hematopoietic stem cells or "HSCs", progenitor cells, or progeny thereof.

The present invention relates to methods using base editors for efficiently genetically engineer cells, especially primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the invention is directed to rules for designing highly active and specific TALE-base editors displaying improved on-target / off-target activity ratios useful to manufacture complex gene edited cells of therapeutic grade or to perform in-vivo gene therapy. The resulting TALE-base editors can be used alone or in combination with rare-cutting endonucleases in various gene therapy approaches.

Combination treatments are provided that result in synergistic effects in the treatment of a disease selected from cancer or infectious diseases. [Solution] A method for treating a disease selected from cancer or infectious disease, comprising administering to a subject having the disease one or more immune checkpoint inhibitors in an amount effective to treat the disease, and administering hematopoietic stem cells to the subject, preferably further comprising administering to the subject a hematopoietic stem cell mobilizing agent.

In the various aspects and embodiments, the present disclosure provides cell populations or cell “banks” thereof (e.g., cell collections) to provide immune compatible, allogeneic cell therapies covering global, ethnic, and disease-specific populations. In the various aspects and embodiments, the cell banks and progeny thereof maintain sufficient HLA Class I and HLA Class II functionalities, while facilitating patient matching to prevent or reduce graft versus host disease (GVHD) or graft rejection. The disclosure further provides methods for creating the cell banks by gene editing, and methods for cell therapy involving cells or tissues derived from the cell banks (including but not limited to hematopoietic stem cells, or “HSCs”, progenitors, or progenies thereof).

The invention discloses a semi-solid culture medium for inducing cell colony growth, which is composed of IMDM culture medium, methylcellulose, fetal bovine serum, induction factors and additives; methylcellulose is added in the form of methylcellulose mother liquor, and is prepared by the following method: (1) taking pure water, heating in a water bath at 80-98°C, adding methylcellulose powder, and stirring to disperse and wet the methylcellulose powder; (2) continuing water bath heating for 10-20 minutes; (3) autoclaving; (4) cooling to room temperature and standing for 16-24 hours; (5) standing at 4°C for 16-24 hours, inverting and mixing, and obtaining methylcellulose mother liquor. The semi-solid culture medium for inducing cell colony growth of the invention adopts a specific method to prepare methylcellulose mother liquor, so that methylcellulose dissolves more fully, is more conducive to colony formation, and can be used for culturing and detecting hematopoietic stem cells, and for inducing the growth of monocytes, granulocytes, and erythroid cell colonies.

The present invention provides an application of the TADA1 gene in enhancing the expression of fetal hemoglobin, which relates to the field of biotechnology. The present invention discovers a new therapeutic target, TADA1. After knocking out the TADA1 gene in HUDEP2 cells and hematopoietic stem cells by gene editing technology, it is found that the edited cells can significantly increase the expression levels of γ-globin and fetal hemoglobin (HbF), and promote erythroid differentiation. Applying substances that down-regulate the level of the TADA1 gene or its expression product includes using them in the preparation of products for enhancing the expression of fetal hemoglobin in a subject, providing a new drug target.

The present invention relates to a biological sample bank comprising at least two cell biological sample banks wherein the cells of the cell biological sample bank may be immune cells or hematopoietic stem and progenitor cells (HSPC) or in vitro produced T cell progenitor cells wherein the cells of each cell bank have a specific homozygous human leukocyte antigen (HLA) haplotype. The invention also relates to a method for selecting at least one cell bank, and to the use of the selected cell bank as an agent, in particular for the treatment of immunodeficiencies, immune disorders and / or diseases, lymphopenia or cancer, and covering a large number of patients.

Materials, methods, and systems for the cellular redifferentiation and expansion of induced pluripotent stem cell (iPSC)-derived hematopoietic stem cells (iHSCs) without the use of serum or additional cells is provided.

The present invention relates to a method for efficiently genetically engineering cells, in particular primary hematopoietic stem cells (HSCs) and primary immune cells, using a base editor. In particular, the present invention relates to rules for designing a highly active and specific TALE-base editor exhibiting an improved on-target / off-target activity ratio for use in the manufacture of therapeutic levels of complex gene editing cells or in vivo gene therapy. In various gene therapy methods, the resulting TALE-base editor can be used either alone or in combination with a rare-cleavage endonuclease.

The utility model relates to the technical field of hematopoietic stem cell storage, in particular to a hematopoietic stem cell blood bag cryopreservation box which comprises a box body. The placing mechanism is arranged on the box body, the placing mechanism comprises two fixing blocks and a plurality of fixing boxes, through cooperation of a fixing frame, a hasp lock and the like, the multiple fixing boxes can be conveniently limited and fixed, cooperation of the fixing boxes, a cover plate, a protection cushion and the like is facilitated, blood bags are clamped and placed, and damage caused by collision of the blood bags is avoided; one blood bag can be independently taken out conveniently when the blood bags are taken out, a large amount of nitrogen is prevented from being released, nitrogen is further saved, through cooperation of a spring, a limiting block, a pull ring and the like, a cover plate can be conveniently limited and fixed, people can conveniently open or close the cover plate, then the blood bags are taken out, practicability is improved, liquid nitrogen is injected into a liquid nitrogen box through a liquid inlet, and use is convenient. Nitrogen can conveniently penetrate through the multiple air holes to freeze the two sides of the blood bag, and the freezing effect of the blood bag is guaranteed.

The present invention relates to a conditioning regimen for the transplant of a cell to a subject, optionally wherein the cell is a hematopoietic stem / progenitor cells (HSPC), a CAR cell or a platelet. The invention also relates to methods for the prevention or treatment of a disease or condition in a subject by administration of a cell transplant, wherein said administration comprises the conditioning regimen of the invention.

To provide genetically modified cells and uses thereof.SOLUTION: The present invention generally relates to a population of stem cells (e.g., iPSCs or HSCs) comprising a T cell receptor and a nucleic acid encoding a chimeric antigen receptor directed to a plurality of distinct antigenic determinants, e.g., two distinct tumor antigenic determinants. The present invention is also directed to a population of T cells co-expressing a T cell receptor and a chimeric antigen receptor directed to multiple distinct antigenic determinants, such as two distinct tumor antigenic determinants. The cells of the invention may be derived from selected donors whose HLA type matches a significant sector of the population, and are useful in a variety of applications, particularly in the context of therapeutic treatment of neoplastic conditions.SELECTED DRAWING: None