400 results about "Hematopoietic stem cell" patented technology

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 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.

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 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.

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.

Production and maintenance of hematopoietic stem cells in in vitro culture systems has proven to be elusive. Disclosed herein are hematopoietic stem cell compositions that originate from organoids such as liver organoids. These organoids also comprise a rare type of immune cell that is not yet fully elucidated due to the difficulty in isolating said immune cell from biological samples. Also disclosed herein are methods of producing said hematopoietic stem cells and immune cells from organoids, as well as methods of expanding hematopoietic stem cells from other sources using these organoids.

In aspects, the present disclosure provides a recombinant fusion protein comprising, consisting essentially of, or consisting of (a) a rhabdoviral G glycoprotein or a functional fragment or derivative thereof and (b) a targeting molecule, wherein the targeting molecule targets the recombinant fusion protein to a hematopoietic stem cell (HSC). Additional aspects are as described herein.

Genetically engineered cells (e.g., HSPCs or T cells) having one or more genetically edited cell surface protein genes, such as hematopoietic stem cells, and therapeutic uses thereof, alone or in combination with immunotherapy targeting the cell surface proteins.

The invention belongs to the technical field of biomolecular markers, and particularly relates to a cross-animal general skeleton-derived hematopoietic stem cell marker gene set and a screening method thereof. According to the invention, a bone-derived hematopoietic stem cell marker gene set universal across animal categories is constructed for the first time, and the bone-derived hematopoietic stem cell marker gene set comprises at least five of Cdc42, Cbx, Tfam, Denr, Mcts1, Ak2, Ruvbl, Ahcy, Nna and Vdac; the hematopoietic stem cell marker gene set is obtained through cross-species homologous gene screening, the defect that a traditional vertebrate marker has no orthohomology in invertebrates is overcome, accurate recognition of HSC in shells is achieved, the hematopoietic stem cell marker gene set has species universality and cell specificity, the immune state of aquatic animals can be evaluated, disease-resistant breeding can be guided, and the application prospect is wide. And molecular evidence is provided for analyzing an evolution path of a hematopoietic system from invertebrates to vertebrates.

In certain embodiments methods of treating X-Linked agammaglobulinemia (XLA) in a mammal are provided where the methods comprise: i) providing differentiated T cells and / or stem / progenitor cells from the mammal; ii) performing a targeted insertion of a corrective BTK cDNA at the BTK gene locus in said cells to provide a corrected BTK gene in said cells; and iii) introducing said cells into said mammal where said corrected BTK gene is expressed in a physiologically regulated manner.

A composition comprising a naphthoquinone-based compound as an active ingredient and uses thereof are disclosed. The composition is effective for preventing or ameliorating fatigue, cachexia, pain, cognitive decline, and hematopoietic stem cell reduction which are side effects related to anticancer drug treatment. The naphthoquinone-based compounds, dunnione and β-lapachone, reduce the secretion and production of inflammatory cytokines which are increased by the anticancer drug treatment, and prevent fatigue, cachexia, cognitive decline, and hematopoietic stem cell reduction which are side effects associated with anticancer drug treatment.

The utility model provides a kind of hematopoietic stem cell liquid nitrogen transfer tank, it is related to the technical field of liquid nitrogen transfer tank.The hematopoietic stem cell liquid nitrogen transfer tank includes tank body, and the bottom surface of the tank body is fixedly connected with output port.The hematopoietic stem cell liquid nitrogen transfer tank is matched between output port, storage tank, gas outlet pipe and storage bag, when liquid nitrogen evaporates, the pressure in the tank body is increased, the moving plate will be moved downward, spring is compressed, telescopic rod is shortened, the moving plate will be separated from the screw pipe, gas enters the inside of storage tank, then enters storage bag through gas outlet pipe, nitrogen is stored, the pressure in the tank body is reduced, the problem that the liquid nitrogen transfer tank needs to be frequently opened and closed during use to take out or add hematopoietic stem cells is solved, a part of liquid nitrogen will evaporate and expand when tank cover is opened each time, if the gas cannot be effectively discharged, the pressure in the tank body may be sharply increased in a short time.

In the various aspects and embodiments, the present disclosure provides cell populations or cell "banks" thereof to provide immune compatible, allogeneic cell therapies. In the various aspects and embodiments, the cell populations 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 populations by gene editing, and methods for cell therapy involving cells or tissues derived from the cell populations (including but not limited to hematopoietic stem cells, or "HSCs", progenitors, or progenies thereof).

The invention provides a preparation method of a novel mesenchymal stem cell (MSC) and application of the MSC in HSC culture, and belongs to the field of mesenchymal stem cell culture, and the MSC provided by the invention is used for promoting a support function of a hematopoietic stem cell (HSC). The MSC culture medium provided by the invention can generate higher HSC support factor expression and has a stronger HSC support function.

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 disclosure provides lipid assemblies suitable for delivery of therapeutic agents to hematopoietic stem and progenitor cells (HSPCs), wherein the lipid assemblies comprise a neutral polymer surface lipid. The present disclosure also provides therapeutic and diagnostic uses related to the lipid assemblies.

The present disclosure provides methods for producing modified HSCs, wherein the method comprises passing a cell suspension comprising the cell and a payload through a constriction, wherein the constriction deforms the cell, thereby causing a perturbation of the cell such that the payload enters the cell. In some aspects, the payloads are capable of enhancing one or more properties of the HSCs, such that the HSCs are better engrafted within the bone marrow of a subject.

The utility model belongs to the technical field of medical instruments, and discloses a bone marrow blood cell filtering and collecting device which comprises a support, a collecting pipe, a net barrel and a blood product bag, the collecting pipe is detachably arranged on the support and is of a barrel-shaped structure with an opening in the top, a liquid outlet connector is arranged at the bottom of the collecting pipe and detachably connected with a liquid outlet pipe, and the liquid outlet pipe is connected with the net barrel. A liquid stopping clamp is arranged on the liquid outlet pipe; the net cylinder is of a cylindrical structure with a top opening, the net cylinder is arranged in the collecting pipe, the edge of the top opening of the net cylinder is provided with a connecting part, and the connecting part is detachably connected with the top opening of the collecting pipe; the blood product bag is detachably connected with the end, away from the liquid outlet connector, of the liquid outlet pipe. According to the bone marrow blood cell filtering and collecting device, impurities in bone marrow blood can be effectively filtered out, the purposes of separating bone marrow stem cells, reducing waste of the bone marrow blood cells and conveniently transferring the bone marrow blood cells into a blood product bag by an operator are achieved, and the quality of the collected bone marrow blood cells and the hematopoietic stem cell infusion effect are improved.

The invention discloses an osteoclast culture method as well as a culture medium and application thereof, the culture method is based on primary monocyte extraction, inoculation is performed according to a specific density, then quantitative M-CSF is added, and culture is performed overnight; on the second day, when the cell confluence degree of the mononuclear bone marrow hematopoietic stem cells is 5-30%, supplementing quantitative RANKL into each hole, continuously culturing for 2-4 days, then changing the solution, and obtaining mature osteoclasts on the sixth-seventh day. According to the invention, the optimization relationship among the cell activity, the cell density and the culture medium in the primary culture process of the osteoclast is deeply studied, and from the perspective of cost reduction and efficiency improvement, the use cost of cell factors is remarkably reduced, the number of times of liquid change is reduced, and the traditional culture time of 10-12 days (calculated from cell extraction) is shortened to 6-7 days. The average diameter of the mature osteoclast cultured by the method is larger, the number of fused cell nucleuses is larger, the space proportion of the mature osteoclast is not less than 80%, and the cell quality is obviously higher than that in the prior art.

Provided are: an adeno-associated virus (AAV) vector, the AAV vector comprising a cytokine gene, and the cytokine being selected from any one or two or more of the following: IL3, GM-CSF, IL6, APRIL, and BAFF; an AAV vector combination comprising any two or three or more of said AAV vectors; and a method for constructing an acute myeloid leukemia xenograft non-human animal and a method for constructing a multiple myeloma xenograft non-human animal. In addition, further provided is another adeno-associated virus (AAV) vector, the AAV vector comprising a cytokine gene, and the cytokine being selected from any one or two or more of the following: IL2, IL3, IL6, IL15, THPO, SCF, and GM-CSF; further provided is an AAV vector combination comprising any two or three or more of said AAV vectors; and further provided is the use of the AAV vector and AAV vector combination in the construction of a humanized immune system non-human animal, as well as a method for constructing a humanized immune system non-human animal and a method for promoting the differentiation of human hematopoietic stem cells into CD14+ monocytes and CD66b+ granulocytes.

Methods and compositions relating to the treatment of degenerative disc disease are provided.SOLUTION: In some embodiments, cannabidiol is utilized to enhance the therapeutic and / or regenerative activity of fibroblasts. In other embodiments, cannabidiol is utilized to augment the reparative effects of other regenerative cells, including monocytes, mesenchymal stem cells, and / or hematopoietic stem cells. In some embodiments, cannabidiol is utilized in the culture media of regenerative cells prior to administration of said cells.SELECTED DRAWING: Figure 1

The present invention relates to methods for treating diseases by the in vivo gene editing of hematopoietic stem and progenitor cells (HSPCs), and in particular to the use of a CXCR4 antagonist to increase the efficiency of HSPC gene editing in vivo when administered prior to or in conjunction with administration of a gene editing system to a subject in need thereof.

The present invention discloses a method for constructing a gene regulatory network based on a generative flow network, comprising the following steps: conducting experiments on the sc-RNA-seq dataset of mouse hematopoietic stem cells to evaluate the performance of constructing a gene regulatory network. Using a sparse Transformer to perform sparse feature extraction on the scRNA-seq data to facilitate more accurate subsequent construction of a gene regulatory network; after the sparse feature extraction, inputting the sparse features into a generative flow network model for constructing a gene regulatory network. Through multiple iterative updates of the generative flow network model, a probability distribution of gene regulatory relationships associated with the scRNA-seq dataset of mouse hematopoietic stem cells is obtained, and the final gene regulatory network is extracted by setting a regulatory extraction threshold. The present invention effectively alleviates the problem that existing methods are difficult to capture complex gene regulatory relationships from sparse scRNA-seq data, and can be used as an effective tool to provide reference for medical researchers to analyze gene regulatory mechanisms.