744 results about "Hematopoietic stem cell" patented technology

The present disclosure provides compositions and methods for the selective transduction and genome editing of human cells (e.g., hematopoietic stem and progenitors cells, HSPCs) using engineered viral like particles (eVLPs). Aspects of the disclosure provide eVLP compositions comprising fusion proteins comprising a targeting moiety. In some embodiments, the fusion proteins comprise a cytokine conjugated to a transmembrane protein and / or an envelope glycoprotein. In other embodiments, the fusion proteins comprise a targeting moiety domain, a stalk protein domain, a transmembrane and / or envelope glycoprotein domain. Targeted-eVLP architectures comprising various targeting domains, stalk domains, transmembrane domains, and envelope glycoproteins are also provided herein. Other aspects of the disclosure provide eVLP compositions comprising envelope glycoproteins comprising non-natural sugars and methods of conjugating said eVLPs to various targeting moieties using bio-orthogonal click chemistry. Polynucleotides, vectors, cells, and kits useful for producing the articles, and performing the methods, described herein are also provided.

The invention discloses a micro-fluidic optical sensor real-time hematopoietic stem cell detection device which comprises a micro-fluidic chip, an optical sensing system and a data processing unit.The micro-fluidic chip is used for guiding a blood sample, an optical detection mode of optical turbidity measurement is combined, the detection speed and the detection accuracy are increased, and the detection accuracy is improved. The concentration of the hematopoietic stem cells can be monitored in real time, instant data are provided, and clinical instant decision making is supported. The method is simple and convenient to operate, does not need complex equipment or a long-time treatment process, and is suitable for a POCT environment. By combining a microfluidic technology and an optical sensor, the detection accuracy of the cell concentration is improved, and the influence of interference factors is reduced. Compared with flow cytometry equipment, the device is simple in structure and can be designed in a miniaturized manner, so that the device is suitable for clinical sites or other instant detection environments. And by using the micro-fluidic chip and the low-energy-consumption optical sensor, the influence on the environment is reduced.

The present disclosure provides bispecific stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., hematopoietic stem cells, to modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

Described herein are methods for inducing HSC specification in a cell. Aspects of the invention relate to contacting a cell with a Runx1-CBFβ inhibitor for a specified period of time, and then removing the inhibitor from the cell. In some embodiments of any of the aspects, HSC specificity is maintained long-term.

The invention relates to the technical field of stem cells, in particular to a lentivirus envelope plasmid combination and application thereof, a lentivirus and a packaging method thereof and a method for transduction of hematopoietic stem cells. The invention provides an envelope plasmid combination for lentivirus packaging, which is composed of lentivirus packaging plasmids containing VSVG glycoprotein and lentivirus packaging plasmids containing BaEV glycoprotein in a ratio of 3: 7. The invention further provides a method for transduction of the hematopoietic stem cells by the lentivirus, the method is simple and convenient to operate, the long-term dryness of the hematopoietic stem cells in vitro can be maintained, efficient and stable transduction of the hematopoietic stem cells can be realized, and the transduction rate is greater than 90%. The lentivirus transduction method hematopoietic stem cells can be used for hematopoietic stem cell gene therapy hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome and the like, and the application prospect is good.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The present invention relates to a bispecific chimeric antigen receptor targeting CD117 and CD7 and its application, wherein the bispecific chimeric antigen receptor comprises a signal peptide, an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain, wherein the antigen binding domain comprises a CD117 binding domain and a CD7 binding domain. The bispecific chimeric antigen receptor provided by the present invention combines targeted antibodies for CD117 and CD7 together, recognizes and binds to two different antigens at the same time, enhances the targeted elimination ability of malignant cells, and by acting on hematopoietic stem cells and immune cells at the same time, can more effectively eliminate tumor cells in the receptor, while retaining or reconstructing normal hematopoietic and immune functions.

The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem / progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem / progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of naïve conventional αβ-T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.

The invention discloses an application of a compound in preparation of a product for enhancing the metabolic activity of hematopoietic stem cells and treating metachromatic white matter dystrophy. The compound comprises Azoramide. Azoramide is adopted to treat transfected hematopoietic stem cells, and cell apoptosis, cell necrosis and mitochondrial respiration conditions of the hematopoietic stem cells are obviously improved, so that the hematopoietic stem cells are expected to be applied to enhancement of transfection efficiency and metabolic activity of the hematopoietic stem cells transfected by the ARSA gene and reduction of ROS generation, and the effectiveness of the hematopoietic stem cells in treatment of MLD diseases is enhanced.

The invention discloses a cord blood-derived hematopoietic stem cell as well as an amplification method and application thereof. The method comprises the step of culturing umbilical cord blood mononuclear cells by using a culture medium containing thymus active polypeptide, stem cell growth factors and heat shock protein. According to the method for amplifying the umbilical cord blood-derived hematopoietic stem cells, the proliferation efficiency of umbilical cord blood mononuclear cells can be remarkably improved, and the amplification capacity of umbilical cord blood immune cells (NK cells) is improved by more than 5 times compared with that of a traditional method.

Provided herein are modified CD117 polypeptides comprising one or more amino acid modifications that inhibit or reduce binding to an anti-CD117 antibody. Also provided are nucleic acids encoding modified CD117 polypeptides, and cells, e.g., hematopoietic stem cells (HSC), in which the CD117 nucleic acid or polypeptide is introduced. The HSC may be used, for example, in hematopoietic cell transplant.

A method for haematopoietic stem and / or progenitor cell (HSPC) transplantation in a subject in need thereof, comprising the steps: (a) administering one or more HSPC mobiliser to the subject to mobilise the subject's endogenous HSPCs; and (b) administering a population of HSPCs to the subject.

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

The invention relates to a method for efficiently inducing human hematopoietic stem progenitor cell erythroid to be directionally differentiated into mature erythrocytes in a serum-free and feeder-layer-free manner, which adopts a serum-free and feeder-layer-cell-free induction culture system, and uses an mTOR pathway inhibitor rapamycin to regulate the activity of an mTOR pathway in the erythroid differentiation process. The use dosage and the treatment mode of the mTOR pathway inhibitor rapamycin are further optimized, and the erythrocyte denucleation efficiency of an in-vitro induced differentiation system is remarkably improved to 70% under the condition that erythrocyte proliferation and differentiation are not affected or the cell state is not reduced. According to the method, heterologous pollution caused by animal serum or heterologous cells is effectively avoided, the clinical safety of in-vitro preparation of transfusion-level red blood cells in the future is ensured, the erythroid directional induced differentiation final maturation efficiency of the human hematopoietic stem progenitor cells is improved, meanwhile, the reagent cost is reduced, and large-scale preparation and clinical transformation are facilitated.

Disclosed are anti-CD45 antibodies, antigen binding fragments thereof, and antibody drug conjugates (ADCs) that specifically bind to human CD45. Such antibodies and ADCs are useful in therapeutic methods, including methods of depleting CD45+ cells from a patient. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD45+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy, and to improve the engraftment of hematopoietic stem cell transplants, by selectively depleting endogenous CD45+ cells prior to the transplant procedure.

The invention relates to the technical field of cell culture detection, and particularly discloses a mesenchymal stem cell and hematopoietic stem cell in-vitro culture detection method and system.The method comprises the steps that a cell culture environment and culture medium components are analyzed, a cell culture detection reference evaluation value is determined, and whether mesenchymal stem cell and hematopoietic stem cell culture is qualified or not is judged; and analyzing the mesenchymal stem cells and the hematopoietic stem cells which are not qualified in culture to obtain mesenchymal stem cell characteristic values and hematopoietic stem cell characteristic values, and determining a culture adjustment scheme of the unqualified mesenchymal stem cells and the hematopoietic stem cells based on the mesenchymal stem cell characteristic values and the hematopoietic stem cell characteristic values. The problems that traditional mesenchymal stem cell and hematopoietic stem cell culture lacks comprehensive and unified culture and detection standards, and the adaptive capacity of a culture adjustment scheme is insufficient are solved, the healthy state and functions of cells can be kept, and the success rate and efficiency of cell culture can be improved.

The invention discloses a method for analyzing a mechanism of treating leucopenia by using a Shengbai oral liquid by using a network pharmacology mode, and the method is based on an HITS algorithm, and identifies key regulation and control nodes through hub and authority scores of nodes. An analysis result shows that PPBP, ALOXE3 and CCR1 are hub genes ranked in the first three, and PPBP not only has the highest hub score, but also shows the most significant expression change. In a bone marrow microenvironment, PPBP / CXCL7 may affect differentiation and maturation of hematopoietic stem cells and promote generation of specific types of leukocytes.

Described herein are compositions and methods for modifying eukaryotic cells, for example, to express a transgene of interest and / or to produce an expanded population of cells ex vivo. Using the compositions and methods of the disclosure, a population of eukaryotic cells, such as a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) may be transduced to express a gene of interest by contacting the cells with a viral vector, such as a lentiviral vector, and a diblock copolymer, such as a diblock copolymer composed of a hydrophilic region and a hydrophobic region. For example, the diblock copolymer may be composed of polyoxyethylene (PEO) subunits and polyoxypropylene (PRO) subunits. Additionally, the compositions and methods described herein can be used to promote the proliferation or survival of a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) ex vivo, for example, by contacting the cells with a diblock copolymer.

The present disclosure relates to methods of conditioning and / or depleting cell populations in the bone marrow of a subject in need of hematopoietic cell transplantation (HCT), comprising administering an antibody that binds to a target on endogenous hematopoietic stem cells (HSCs) in the subject. In a preferred embodiment, the target is CD 117 (c-kit).

This invention relates to methods and compositions directed to mobilizing a cell in a subject by blocking CXCR4, a beta-adrenergic receptor, a GPCR, or any combination thereof. In some embodiments, the cell is a hematopoietic stem cell. In some embodiments, the method further comprises administration of G-CSF. This invention also relates to methods of treatment, methods for qualifying a subject for treatment, and methods for preparing a subject for treatment, by blocking CXCR4, a beta-adrenergic receptor, a GPCR, or any combination thereof. In some embodiments, the cell is a hematopoietic stem cell. In some embodiments, the treatment is for cancer. In some embodiments, the CXCR4 is GPC-100. In some embodiments, the method further comprises administration of G-CSF.

The present invention provides antibody drug conjugates, wherein an antibody or antibody fragment that specifically binds to human cKIT is linked to a drug moiety, optionally through a linker. The present invention further provides pharmaceutical compositions comprising the antibody drug conjugates; and methods of making and using such pharmaceutical compositions for ablating hematopoietic stem cells in a patient in need thereof.

The present invention provides: a culture medium for culturing hematopoietic stem cells in vitro, the culture medium making it possible to selectively culture hematopoietic stem cells when a cell population containing the hematopoietic stem cells and cancer cells is cultured; and a method for culturing hematopoietic stem cells using the culture medium. The present invention relates to: a culture medium for human cells, the culture medium being intended to be used for culturing a cell population containing human cells, and the culture medium comprising a polyalkylene glycol modified by a copolymer of a polyvinylcaprolactam block and a polyvinyl acetate block, a phosphatidylinositol-3 kinase (PI3K) activator, a TPO receptor agonist, and one or more components selected from the group consisting of a proteasome inhibitor, a TNF-related apoptosis-inducing ligand and a cereblon modulator; and a method for culturing human hematopoietic stem cells, the method comprising culturing a cell population containing human hematopoietic stem cells in the aforementioned culture medium for human cells.

Hematopoietic stem cells (HSC) are essential to developing a functional immune system, including monocyte-macrophage cells required for wound healing. Described herein are methods of using yellow bone marrow as a source of cells to generate hematopoietic stem cells. The methods include expansion of human hematopoietic stem cells by culture of human yellow bone marrow in 3-dimensional hydrogel and pro-angiogenic, stem cell-promoting medium.

There is provided a hydrogel, such as a functionalized hydrogel, for use in the expansion and / or differentiation of cells, that are encapsulated within the three-dimensional structure of the hydrogel. In some aspects of the invention, the hydrogel better mimics the thymus microenvironment than prior hydrogels for T cell expansion and differentiation and can be used in the expansion and differentiation of HSPCs, HSCs or PCs or combinations thereof in the production of T cells, T-cell committed precursors or progenitor cells and in methods for producing mature T cells. Methods of making the hydrogels, methods of culturing the cells in the hydrogel and uses of the hydrogels and cells produced are also described.

The invention discloses a small-molecule compound and application thereof in in-vitro amplification of hematopoietic stem cells and / or progenitor cells. The structural general formula of the small-molecule compound is as shown in formula (I). The series of compounds disclosed by the invention can be used in the medical field of related diseases taking hematopoietic stem cell transplantation as a treatment method, including in-vitro amplification culture of hematopoietic stem cells and progenitor cells from umbilical cord blood, bone marrow and mobilized peripheral blood and culture, maintenance and amplification of genetically modified hematopoietic stem and progenitor cells; meanwhile, the invention is suitable for application of downstream derived cell products generated by hematopoietic stem cell differentiation, including red blood cells, blood platelets, T cells, B cells and NK cells, in drugs for treating related diseases. # imgabs0 #

A cell processing platform and method for selecting and isolating target cells, such as T-cells, NK-cells, or hematopoietic stem cells, from a biological sample using functionalized microbubbles. The platform employs microbubbles with lipid shells, functionalized with streptavidin and biotinylated linkers, to bind specific target cells and render them buoyant within the suspension. A centrifugation module separates non-target cells by sedimentation while maintaining the buoyancy of target cell-microbubble complexes. A pneumatic control system disrupts the microbubbles under controlled pressure or frequency, releasing the target cells for downstream processing without compromising viability. Additional features include a microbubble generation module capable of sequentially functionalizing ligands for multi-step cell selection and a temperature-controlled environment to ensure ligand stability. The system supports non-destructive cell release and sorting, enabling precise, contamination-free, and high-efficiency cell isolation for therapeutic and research applications.

The invention discloses a bionic bone marrow microenvironment assembly for hematopoietic stem cell in-vitro amplification and a preparation method. The bone marrow microenvironment assembly comprises a three-dimensional scaffold and osteoblasts (OBs), wherein the three-dimensional scaffold comprises chitosan (CS) and sodium alginate (Alg) which are prepared into mixed gel, and the mixed gel is freeze-dried to prepare the three-dimensional scaffold; wherein the osteoblasts (OBs) are obtained by culturing and induced differentiation of umbilical cord mesenchymal stem cells (MSCs) inoculated on a three-dimensional scaffold, and the osteoblasts (OBs) as stromal cells and the three-dimensional scaffold jointly form the hematopoietic stem cell in-vitro amplification bionic bone marrow microenvironment assembly; in the hematopoietic stem cell in-vitro amplification bionic bone marrow microenvironment assembly, the preparation of the three-dimensional scaffold comprises the processes of freezing, remelting, freezing, crosslinking, freeze-drying and the like, so that a three-dimensional space form with wrinkles on the pore surface and pore size distribution between 70 microns and 400 microns is generated in the three-dimensional scaffold, and the three-dimensional space form is closer to a real stem cell niche; therefore, the practical application effect of the bionic bone marrow microenvironment assembly for in-vitro amplification of the hematopoietic stem cells is further improved.

The invention discloses a brain glioma animal model construction method based on an AAV mediated immune microenvironment. The method comprises the following steps: selecting an immunodeficient mouse at the right age; human CD34 + hematopoietic stem cells are injected for immune system reconstruction; human CD45 + immune cells in the peripheral blood PBMC are detected; the method comprises the following steps: selecting tumor tissues with high-expression brain glioma marker genes, carrying out rapid qPCR (quantitative polymerase chain reaction) or targeted RNA-seq immunohistochemical multiple verification, and screening consistent tumor tissues; the method comprises the following steps: physically dicing tumor tissues, treating the tumor tissues with pretreatment liquid, digesting the tumor tissues into single-cell suspension, and inoculating the single-cell suspension into a mouse cranium; an AAV vector carrying a specific immune regulation gene is injected into the tail vein of the mouse, and the brain glioma immune microenvironment is regulated; when it is observed that the tumor tissue grows stably and has immune cell infiltration characteristics, construction of the brain glioma animal model is completed. Compared with an existing model, the brain glioma model which is more stable, more scientific and closer to the human immune background is provided, and the brain glioma model is suitable for related immunotherapy drug screening and mechanism research.

Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and / or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

The present invention pertains to periostin compounds for use in the prevention and treatment of haematological complications, such as adverse events from therapy or haematological diseases. In context of the present invention a therapeutic was developed for enhancing haematopoiesis in patients and to support haematopoietic stem cell (HSC) transplantation (HSCT) by administration of periostin compounds to patients or stem cell donors, or by contacting HSC directly with periostin compounds, for example ex vivo, to improve a transplant HSC preparation. The present invention provides periostin derived compounds such as polypeptides, peptides, nucleic acids, and other periostin-derived agents, that are used both in therapeutic applications and for improving haematopoiesis, for example in stem cell donor subjects or to treat HSC in vitro.