272 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 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 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.

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.

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 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 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.

Provided in the present invention is an sgRNA targeting the mouse FLT3 gene. Further provided in the present invention is a method for constructing a mouse having a humanized immune system, the method comprising: injecting an AAV vector comprising a cytokine gene into a severely immunodeficient FLT3-gene-knockout mouse; optionally irradiating the FLT3-gene-knockout mouse; and injecting human hematopoietic stem cells into the FLT3-gene-knockout mouse.

The present disclosure relates to methods, media and supplements for culturing target cells, such as hematopoietic stem and progenitor cells (HSPC). The methods, media, and supplements of the present disclosure may include one or more epigenetic modifiers within culture conditions to culture and / or expand target cells, such as HSPC or CD34 + cells, such as may be obtained, enriched, or isolated from infected / diseased or normal primary samples. Output populations of HSPCs amplified in the presence of one or more epigenetic modifiers may be suitable for use in downstream applications.

Method and systems for sorting potential hematopoietic stem cell transplant (HSCT) donors as a donor or non-donor using immunophenotyping of blood samples. The methods and systems can be used to identify a donor for a HSCT or to choose a donor to generate a HSCT blood product that is not likely to result in bad outcomes for a recipient. Also provided herein are methods and systems for training machine learning models that can be used in methods and systems for sorting potential HSCT donors.

The present invention relates to a new therapeutic approach for treatment of ANCA-associated vasculitis (Anti-neutrophil cytoplasmic autoantibody-associated vasculitis, AAV). It provides an agent for reducing expression of proteinase 3 (PR3) in a cell, in particular, a gene editing compound targeting the proteinase 3 gene, an epigenetic editing compound targeting the proteinase 3 gene, or an expression vector encoding an inhibitory oligonucleotide capable of selectively binding to a target nucleic acid sequence in mRNA encoding proteinase 3, e.g., an inhibitory oligonucleotide capable of inducing RNAi or an antisense oligonucleotide. Further, a method of reducing expression of proteinase 3 in a hematopoietic stem cell or cell derived therefrom, e.g., a neutrophil, is provided, as well as such cells having a reduced expression of proteinase 3. The cells or agents can be used for treating a subject having a proteinase 3-ANCA-associated vasculitis.

The utility model relates to the technical field of biological experiment instruments, in particular to a hanging accessory used in the separation process of umbilical cord blood hematopoietic stem cells, which is mainly used for being connected with a grid at the top of a biological safety cabinet and comprises a fixed end connected with the grid at the top of the biological safety cabinet, and a hook used for being connected with a blood bag is arranged below the fixed end. The fixing end comprises a clamping ring, a torsional spring clamping opening capable of being clamped into a grid is formed in the clamping ring, a limiting sliding groove is formed in the inner side of the clamping ring, and a limiting rod capable of moving up and down along the inner wall of the clamping ring is slidably connected into the limiting sliding groove. A reset spring capable of resetting the limiting rod upwards is arranged between the bottom of the limiting sliding groove and the limiting rod. The technical problems that in the prior art, a blood bag is connected with a grid in a biological safety cabinet through a paper clip, then the blood bag is hung, shaking is large, the blood bag is prone to falling off, a sample possibly needs to be centrifuged many times, and the motility rate of the sample is affected are solved.

The invention relates to the technical field of hematopoietic reconstruction, in particular to application of costal cartilage derived stem cells and costal cartilage derived stem cells combined with pluripotent progenitor cells, hematopoietic stem cells or cyclosporine in preparation of a preparation for hematopoietic reconstruction. The costal cartilage derived stem cells (CD45-CD51 +) are derived from costal cartilage and have remarkable ecological niche recovery capability. When the cells are used alone or combined with hematopoietic stem cells and pluripotent progenitor cells, the hematopoietic function can be enhanced. The costal cartilage-derived stem cells are directionally differentiated into important supporting cells forming bone marrow ecological niche, secrete hematopoietic cell factors and protect hematopoietic stem / progenitor cells. In treatment of aplastic anemia, costal cartilage-derived stem cells and cyclosporin A have a synergistic effect, and immune-mediated bone marrow failure is improved through dual mechanisms. According to the technical scheme, the technical problem that the effect of treating bone marrow failure and promoting hematopoietic reconstruction by hematopoietic stem cell transplantation is not ideal is solved, and a new way is opened up for treating bone marrow failure and blood system diseases.

The present disclosure provides methods for generating hematopoietic progenitor cells. In some embodiments, the methods involve an in vitro or ex vivo cell culture model utilizing rentionic acid signaling for producing hematopoietic progenitor cells from pluripotent stem cells.

The application belongs to the field of biological medicine, and relates to a culture medium for expanding hematopoietic stem cells and application thereof. The application provides a composition comprising DJ001, UM171, SRT3025, ALA and Trolox. The culture medium containing the composition can be used for expanding hematopoietic stem cells, and is especially suitable for expansion culture of LT-HSCs. Increasing the content of LT-HSC cells is the key to improving the long-term implantation success rate of hematopoietic stem cells. The application of the present application has invented a culture medium for specifically expanding LT-HSC cells, which can expand the LT-HSC cells by more than 500 times in 14 days, and has great clinical treatment value.

The present invention discloses a method for generating thymic epithelial progenitor (TEP) cells, hematopoietic stem cells (HSCs), adult tissue progenitor / stem cells, or other progenitor cells derived from human-induced pluripotent stem cells (iPSCs) to overexpress PD-L1 and / or HLA-G. This innovative approach aims to reduce allogeneic rejection by donor immune cells in immunocompetent recipients. By enhancing the immune-modulatory properties of iPSC-derived cells through the overexpression of PD-L1 and / or HLA-G, the invention seeks to improve the engraftment and functionality of these cells. This strategy holds significant potential for restoring thymus function and inducing immune tolerance, offering therapeutic benefits for patients with thymus defects, immune dysfunction, or requiring enhanced immune tolerance for graft acceptance.

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 phosphatidylserine phospholipid. The present disclosure also provides therapeutic and diagnostic uses related to the lipid assemblies.

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.

The present invention relates to an albumin-free serum-free medium and an albumin-free culture method suitable for culturing human hematopoietic stem cells. The present invention discloses a composition of an albumin-free serum-free medium suitable for culturing human hematopoietic stem cells and an albumin-free culture method. According to the present invention, there is provided a method for culturing human hematopoietic stem cells, the method comprising the step of contacting human hematopoietic stem cells with PVA and a PI3K activator.

The present invention relates to the use of a substance that modulates Fibrillarin in the treatment of hemoglobinopathy. Methods and uses for modulating the expression of fetal hemoglobin (HBF) in hematopoietic stem and progenitor cells (HSPCs) by an inhibitor of nucleolar fibrin (FBL) expression or activity, such as RNAi, small molecule compounds or antibodies, for the treatment of hemoglobinopathies.