36 results about "Hematopoietic precursor cell" patented technology

Provided herein are methods for the in vitro maintenance, expansion, culture, and / or differentiation of pluripotent cells, such as human embryonic stem cells (hESC) or induced pluripotent cells (iPSC), into hematopoietic precursor cells or endothelial cells. The pluripotent cells may be maintained and differentiated under defined conditions; thus, the use of mouse feeder cells or serum is not required in certain embodiments for the differentiation of the pluripotent cells into hematopoietic precursor cells or endothelial cells. The resulting hematopoietic precursor cells may be further differentiated into various myeloid or lymphoid lineages.

The invention generally regards methods for providing ematopoietic cells and precursors of hematopoietic cells from a variety of cell sources, such as pluripotent stem cells or somatic cells. Also provided are therapeutic compositions including the provided hematopoietic cells and precursors of hematopoietic cells, and methods of using such for the treatment of subjects.

It is an object of the present invention to provide an immunodeficient animal capable of generating human-derived lymphoid cells, a human-derived lymphoid cell, and a method for producing a human antigen-specific antibody. The means for solving the aforementioned object is: an immature immunodeficient mammal into which human-derived hematopoietic precursor cells have been transplanted, and which is able to generate said human-derived hematopoietic cells or immunocompetent cells; and a method for producing a human-derived antibody, which is characterized in that it comprises recovering immunocompetent cells from the above-described mammal, culturing the immunocompetent cells, and collecting a human-derived antibody from the obtained culture product.

It is an object of the present invention to provide an immunodeficient animal capable of generating human-derived lymphoid cells, a human-derived lymphoid cell, and a method for producing a human antigen-specific antibody.The means for solving the aforementioned object is: an immature immunodeficient mammal into which human-derived hematopoietic precursor cells have been transplanted, and which is able to generate said human-derived hematopoietic cells or immunocompetent cells; and a method for producing a human-derived antibody, which is characterized in that it comprises recovering immunocompetent cells from the above-described mammal, culturing the immunocompetent cells, and collecting a human-derived antibody from the obtained culture product.

The present inventors discovered that the administration of an agonistic minibody (VB22B sc(Fv)2) against the TPO receptor resulted in not only the induction of human megakaryocyte-specific differentiation (increase in platelet precursor cells), but also the engraftment of transplanted hematopoietic stem cells derived from human cord blood (CD34-positive cells) and significant increase in multi-lineage hematopoietic precursor cells. TPO and TPO receptor agonists can be used as agents for promoting the growth of CD34-positive hematopoietic cells or agents for promoting the engraftment of transplanted cells in the bone marrow, which can be effective when administered alone (without using G-CSF and erythropoietin in combination) after hematopoietic stem cell transplantation (in particular, cord blood transplantation). Furthermore, TPO and TPO receptor agonists can be used as agents for promoting the growth and / or differentiation of multilineage hematopoietic precursor cells and agents for promoting the recovery of multilineage hematopoiesis.

The present invention relates to pluripotent stem cells and methods of promoting long term growth of such cells. In particular, the methods described are used to enhance the proliferation of hematopoietic stem cells, hematopoietic precursor cells, hemangioblasts and endothelial stem cells. The present invention also relates to methods of using such cells, comprising introducing such stem cells, into the host. The present invention also relates to pharmaceutical compositions comprising the cells and such compositions may include growth factors or cytokines to allow for further cell growth and / or cellular differentiation. The invention further relates to methods of in vivo administration of a protein or gene of interest comprising transfecting the stem cells grown by the methods described, with a construct comprising DNA which encodes a protein of interest and then introducing the stem cell into the host where the protein or gene of interest is expressed.

The present invention relates to a method of transplanting haematopoietic precursor cells into a subject in need thereof which involves culturing the haematopoietic precursor cells in the presence of a population of cells enriched for STRO-1bright cells. The method of the present invention is useful in the treatment of haematological disorders.

A method of treating a pulmonary disorder or injury in a subject in need thereof is disclosed. The method comprising administering to the subject non-syngeneic pulmonary tissue cells in suspension comprising an effective amount of hematopoietic precursor cells (HPCs) or supplemented with HPCs, wherein the effective amount is a sufficient amount to achieve tolerance to the pulmonary tissue cells in the absence of chronic immunosuppressive regimen. A method of inducing donor specific tolerance in a subject in need of a pulmonary cell or tissue transplantation is also disclosed.

The invention relates to the field of stem cell biology, and discloses a preparation method of natural killer cells differentiated from human pluripotent stem cells. The preparation method comprises the steps of S1, forming an embryoid body; S2, performing directional permanent hematopoiesis differentiation on the embryoid body to obtain hematopoietic precursor cells; and S3, differentiating the hematopoietic precursor cells to obtain natural killer cells. The invention also discloses application of the natural killer cell prepared by the method as a pharmaceutical composition for preventing and / or treating tumors by cells. According to the method, efficient and stable differentiation of the NK cells is achieved, EB adherent differentiation is achieved in the induced differentiation period, TGFB inhibitor treatment is prolonged, 10% or above of CD34+CD45+permanent hematopoietic HPCs can be obtained through rapid induction. The method has the advantages of being efficient, stable, low in cost and suitable for large-scale cell preparation production; and the method is easy and convenient to operate, the NK cells obtained through differentiation have typical NK cell surface marking molecules, the anti-tumor function of the NK cells is superior to that of the NK cells derived from umbilical cord blood, and great scientific research and clinical application potentials are achieved.

The present disclosure generally regards methods and compositions for providing multi-lineage hematopoietic precursor cells from pluripotent stem cells (PSCs). The PSCs comprise an expression construct encoding an ETS / ERG gene, GATA2 and HOXA9. Also provided are methods for providing hematopoietic stem cells capable of long-term engraftment in mammals, such as humans. Further provided are therapeutic compositions including the provided hematopoietic stem cells and precursors of hematopoietic cells, and methods of using such for the treatment of subjects.

The present invention relates to a method of transplanting haematopoietic precursor cells into a subject in need thereof which involves culturing the haematopoietic precursor cells in the presence of a population of cells enriched for STRO-1bright cells. The method of the present invention is useful in the treatment of haematological disorders.

The present inventors discovered that the administration of an agonistic minibody (VB22B sc(Fv)2) against the TPO receptor resulted in not only the induction of human megakaryocyte-specific differentiation (increase in platelet precursor cells), but also the engraftment of transplanted hematopoietic stem cells derived from human cord blood (CD34-positive cells) and significant increase in multi-lineage hematopoietic precursor cells. TPO and TPO receptor agonists can be used as agents for promoting the growth of CD34-positive hematopoietic cells or agents for promoting the engraftment of transplanted cells in the bone marrow, which can be effective when administered alone (without using G-CSF and erythropoietin in combination) after hematopoietic stem cell transplantation (in particular, cord blood transplantation). Furthermore, TPO and TPO receptor agonists can be used as agents for promoting the growth and / or differentiation of multilineage hematopoietic precursor cells and agents for promoting the recovery of multilineage hematopoiesis.

The invention relates to a culture medium and a method for inducing pluripotent stem cells to differentiate into hematopoietic precursor cells. Specifically, the method comprises the following steps: 1) preparing hematopoietic endothelial precursor cells by a method of differentiating human pluripotent stem cells to generate the hematopoietic endothelial precursor cells; and 2) preparing the hematopoietic precursor cells by a method for promoting the hematopoietic endothelial precursor cells to differentiate into the hematopoietic precursor cells. In the preparation process, the culture medium is adopted, a random rotation mode is adopted for culture, the excellent effective efficiency is obtained, and components of the culture medium are definite.

Provided herein are methods for the efficient in vitro differentiation of HLA homozygous blood cell-derived pluripotent stem cells to hematopoietic precursor cells, and the further differentiation of the hematopoietic precursor cells into HLA homozygous immune cells of various myeloid or lymphoid lineages, particularly T cells, NK cells, and dendritic cells. The pluripotent cells may be maintained and differentiated under defined conditions; thus, the use of mouse feeder cells or serum is not required in certain embodiments for the differentiation of the hematopoietic precursor cells.

Immortalized human stromal cell lines sustain and expand human hematopoietic precursor cells. The precursor cells are obtained from a blood product and inoculated into a culture medium conditioned by exposure to a human stromal cell line. Preferred human stromal cell lines secrete SCF, LIF, MIP1α, and IL-6, as exemplified by a human stromal cell line designated HS-1. The conditioned culture medium may be supplemented with additional growth factors, such as interleukin-3. After expansion the human hematopoietic precursor cells are harvested and returned to a patient or frozen and stored. The immortalized human stromal cell lines can also be used as feeder layers in ex vivo bone marrow cultures or in colony forming assays.

Provided herein are methods for the efficient in vitro differentiation of somatic cell-derived pluripotent stem cells to hematopoietic precursor cells, and the further differentiation of the hematopoietic precursor cells into immune cells of various myeloid or lymphoid lineages, particularly T cells, NK cells, and dendritic cells. The pluripotent cells may be maintained and differentiated under defined conditions; thus, the use of mouse feeder cells or serum is not required in certain embodiments for the differentiation of the hematopoietic precursor cells.

The object of the present invention is to develop a technique in which NK cells having a high cytotoxic activity can be prepared with high purity from hematopoietic precursor cells without using a serum or feeder cells of an animal.A method for expanding NK cells includes the steps of expanding hematopoietic precursor cells under a single culturing condition using a medium supplemented with IL-15, SCF, IL-7 and Flt3L, and differentially inducing the cells obtained in the expanding step into NK cells under a culturing condition using a medium supplemented with IL-2. A pharmaceutical composition contains the NK cells prepared by the method for expanding NK cells of the present invention. The pharmaceutical composition of the present invention is used for treating an infectious disease and / or a cancer.

The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.

The present disclosure generally regards methods and compositions for providing multi-lineage hematopoietic precursor cells from pluripotent stem cells (PSCs). The PSCs comprise an expression construct encoding an ETS / ERG gene, GATA2 and HOXA9. Also provided are methods for providing hematopoietic stem cells capable of long-term engraftment in mammals, such as humans. Further provided are therapeutic compositions including the provided hematopoietic stem cells and precursors of hematopoietic cells, and methods of using such for the treatment of subjects.

The invention discloses a method for preparing CD19-targeted chimeric antigen receptor NK cells from human pluripotent stem cells and application of the CD19-targeted chimeric antigen receptor NK cells. Specifically, the invention discloses the method for preparing CD19-CAR-NK cells, which comprises the following steps: directionally knocking a CD19-CAR gene and an EF1 alpha promoter into a human pluripotent stem cell genome AAVS1 region by utilizing a CRISPR / CAS9 system of a targeted AAVS1 site to obtain recombinant human pluripotent stem cells (CD19-CAR-hPSC), then inducing and culturing the CD19-CAR-hPSC to differentiate into embryoid bodies, sorting CD34+ hematopoietic precursor cells from hematopoietic precursor cells differentiated from the embryoid bodies, then directionally differentiating to the NK cells, and finally differentiating into the CD19-CAR-NK cells. The CD19-CAR-NK cells disclosed by the invention has higher multiplication capacity, higher purity and stronger anti-tumor capacity, and can be safely and effectively used for tumor immunotherapy.

The invention provides application of CD61 as a hematopoietic endothelial cell marker as well as a kit and a method for detecting hematopoietic endothelial cells. The kit comprises a reagent for specifically recognizing the CD61. In a hematopoietic differentiation process, the endothelial cells of CD61<+> have potency of generating hematopoietic precursor cells, namely the endothelial cells of the CD61<+> are hematopoietic endothelial cells. The kit and the method, for detecting the hematopoietic endothelial cells, provided by the invention have the effect of detecting the hematopoietic endothelial cells in the endothelial cells in the hematopoietic differentiation process quickly, sensitively and accurately.

Methods of differentiation of pluripotent stem cells into hematopoietic precursor cells, wherein the method is carried out under suspension agitation, and wherein a GSK-3-inhibitor or a Wnt pathway activator is added during a stage of mesoderm induction, and cell culture media for use in the methods, as well as kits for performing the same.

A method for detection of a precursor T cell or precursor B cell, a method for evaluation of the property of a hematopoietic precursor cell in a source for transplantation, and a kit for use in the evaluation are disclosed. A precursor T cell or precursor B cell can be detected by co-cultivating a stromal cell line with a monocyte. By using the detection method, a precursor T cell or precursor B cell can be quantified and can also evaluate the property of a hematopoietic precursor cell in a source for transplantation.

The invention generally regards methods for providing hematopoietic cells and precursors of hematopoietic cells from a variety of cell sources, such as pluripotent stem cells or somatic cells. Also provided are therapeutic compositions including the provided hematopoietic cells and precursors of hematopoietic cells, and methods of using such for the treatment of subjects.

The present invention provides a novel peptide that can be effectively used to produce or grow tissue-specific stem cells or tissue-specific progenitor cells in vitro. The peptide of the invention is a peptide having an amino acid sequence consisting of the amino acid residues set forth in SEQ ID NO:1, or an analog thereof. A feature of the peptide of the invention is having at least one of the following effects: (1) an effect of inhibiting differentiation of hematopoietic stem cells or hematopoietic progenitor cells into myeloid cells, (2) an effect of promoting amplification of mesenchymal stem cells, and (3) an effect of inducing hematopoietic stem cells from pluripotent stem cells.

The present invention provides a novel peptide that can be effectively used to produce or grow tissue-specific stem cells or tissue-specific progenitor cells in vitro. The peptide of the invention is a peptide having an amino acid sequence consisting of the amino acid residues set forth in SEQ ID NO:1, or an analog thereof. A feature of the peptide of the invention is having at least one of the following effects: (1) an effect of inhibiting differentiation of hematopoietic stem cells or hematopoietic progenitor cells into myeloid cells, (2) an effect of promoting amplification of mesenchymal stem cells, and (3) an effect of inducing hematopoietic stem cells from pluripotent stem cells.