70 results about "Hematopoietic progenitor" patented technology

The invention is in the area of pleuripotent stem cells generated from adipose tissue-derived stromal cells and uses thereof. In particular, the invention includes isolated adipose tissue derived stromal cells that have been induced to express at least one phenotypic characteristic of a neuronal, astroglial, hematopoietic progenitor, or hepatic cell. The invention also includes an isolated adipocyte tissue-derived stromal cell that has been dedifferentiated such that there is an absence of adipocyte phenotypic markers.

The present invention provides a method for producing mature and stable dendritic cells or immature dendritic cells which comprises cultivating hematopoietic progenitor cells in a sterile cultivating apparatus, an apparatus suitable for said method and a method for preparing peripheral blood mononuclear cells, which are suitable for cultivation of dendritic cells.

Pluri-differentiated human mesenchymal progenitor cells (MPCs) are isolated. A method isolates and purifies human mesenchymal progenitor cells from Dexter-type cultures for characterization of and uses, particularly therapeutic uses for such cells. Specifically, isolated MPCs can be used for diagnostic purposes, to enhance the engraftment of hematopoietic progenitor cells, enhance bone marrow transplantation, or aid in the treatment or prevention of graft versus host disease.

Described are compositions and methods relating to gene therapy, particularly as applied to hematopoietic progenitor (HP) cells, to transduced cells and methods of obtaining them, and to methods of using them to provide prolonged engraftment of modified hematopoietic cells in human subjects. The invention particularly relates to ex vivo gene therapy of HP cells for treatment or prevention of HIV infection.

The present invention provides isolated pluri-differentiated human mesenchymal progenitor cells (MPCs), which simultaneously express a plurality of genes that are markers for multiple cell lineages, wherein the multiple cell lineages comprise at least four different mesenchymal cell lineages (e.g., adipocyte, osteoblast, fibroblast, and muscle cell) and wherein each of the markers is specific for a single cell lineage. The present invention also method for isolating and purifying human mesenchymal progenitor cells from Dexter-type cultures for characterization of and uses, particularly therapeutic uses for such cells. Specifically, isolated MPCs can be used for diagnostic purposes, to enhance the engraftment of hematopoietic progenitor cells, enhance bone marrow transplantation, or aid in the treatment or prevention of graft versus host disease.

The present invention relates to methods for deriving human hematopoietic progenitors, primitive macrophages, and microglial cells from human pluripotent stem cells. In particular, provided herein are highly efficient and reproducible methods of obtaining human primitive macrophages and microglia from human pluripotent stem cells, where the primitive macrophages and microglia can be suitable for clinically relevant therapeutic applications.

It is an object of the present invention to provide a method for efficiently preparing blood cells, such as mature megakaryocytes and platelets, from iPS cells in an in vitro culture system.The present invention provides a sac-like structure enclosing hematopoietic progenitor cells, which is obtained by inoculating iPS cells onto feeder cells and then culturing the iPS cells under conditions suitable for inducing the differentiation of hematopoietic progenitor cells. Moreover, the present invention also provides a method for producing various types of blood cells, which comprises culturing hematopoietic progenitor cells enclosed in the sac-like structure under conditions suitable for inducing the differentiation of blood cells. Furthermore, the present invention also provides a method for producing various types of blood cells, particularly megakaryocytes and platelets, without involving the sac-like structure.

Described are compositions and methods relating to gene therapy, particularly as applied to hematopoietic progenitor (HP) cells, to transduced cells and methods of obtaining them, and to methods of using them to provide prolonged engraftment of modified hematopoietic cells in human subjects. The invention particularly relates to ex vivo gene therapy of HP cells for treatment or prevention of HIV infection.

The invention discloses a preparation method for hematopoietic progenitor cells and a special medium for the same. The invention provides the medium for hematopoietic progenitor cells prepared through differentiation of human embryonic stem cells or induced pluripotent stem cells, and the medium comprises cell culture fluid I, cell culture fluid II, cell culture fluid III and cell culture fluid IV. According to results of experiments in the invention, a novel system which has definite components and induces differentiation of human embryonic stem cells step by step to generate hematopoietic progenitor cells is established; the system provides a good research platform for further research of differentiation and generation of hematopoietic stem / progenitor cells and provides a differentiation method for obtaining hematopoietic progenitor cells which can be used in treatment of clinical blood diseases since the differentiation system utilizes serum-free and murine-free stromal cells and the like.

The present invention provides useful means in an expansion culture system for a hematopoietic cell (hematopoietic stem cell, hematopoietic progenitor cell). Specifically, the present invention provides a composition for expanding a hematopoietic cell (hematopoietic stem cell, hematopoietic progenitor cell) containing recombinant human serum albumin; a serum-free medium for expanding a hematopoietic cell containing a basal medium and recombinant human serum albumin; a method of expanding a hematopoietic cell comprising culturing a hematopoietic cell in a serum-free medium containing recombinant human serum albumin, and a culture of a hematopoietic cell that can be obtained by the expansion method.

Recombinant lentiviral vectors having a region encoding a functional β-globin gene; and large portions of the β-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of β-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including β-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.

Disclosed is an autologous non-human mammalian model system derived from induced pluripotent stem (iPS) cells. Also disclosed are methods of differentiating non-human primate iPS cells, which can result in populations of cells enriched for SOX2+ or PDX1+ foregut-like cells, for CDX2+ hindgut-like cells, for CD34+ hematopoietic progenitor-like cells, or epithelial-like cells. Also disclosed is a non-human primate containing an autologous cell type of interest, which is differentiated in vitro from an induced pluripotent stem cell reprogrammed from a primary somatic cell. Methods of monitoring exogenously introduced cells within a non-human mammal are also disclosed.

The present invention relates to the use of compounds of a cannabinoid nature for inhibiting viability with increasing doses of myeloma cell lines. Furthermore, said compounds have been shown not to affect CD34+ cells (normal hematopoietic progenitors) in terms of viability and proliferation. For this reason, the invention paves the way for the use of compounds of a cannabinoid nature as a promising therapy against multiple myeloma and related diseases.

There is described herein a method of enriching a population of stem cells for hematopoietic progenitors. The method comprises inducing hematopoietic differentiation in a population of human embryonic stem cells or human induced pluripotent stem cells; sorting the population based on expression of CD43 and at least one of CD34, CD31 and CD144; and selecting a fraction that is at least one of CD34+CD43-, CD31+CD43- and CD144+CD43-. Also provided are populations of hematopoietic progenitors obtained by the methods described herein.

There is provided an isolated pluri-differentiated human mesenchymal progenitor cells (MPCs), a method for isolating and purifying human mesenchymal progenitor cells from Dexter-type cultures, and characterization of and uses, particularly therapeutic uses for such cells. Specifically, there is provided isolated MPCs which can be used for diagnostic purposes, to enhance the engraftment of hematopoietic progenitor cells, enhance bone marrow transplantation, or aid in the treatment or prevention of graft versus host disease.

The invention discloses a pluripotent stem cells directional differentiation method. The method is characterized in that pluripotent stem cells are cultured under cell culture environment of non exogenous hematopoietic cytokines, non serum, non matrix cells and clear component, after embryoid is formed, a vascular endothelial growth factor and bone morphogenetic protein 4 are added, the embryoid is attached on the surface spread with collagen IV, mesoderm differentiation is induced, and hemopoietic progenitor cells and blood corpuscles are generated. The cell culture system with determined component enables directional differentiation on the pluripotent stem cells, has the advantages of low cost, simple operation, high repeatability and ordered differentiation process, can massively generate hemopoietic progenitor cells and blood corpuscles, and has important meaning for researching a blood growth process mechanism.

A method for efficiently preparing blood cells, such as mature megakaryocytes and platelets, from iPS cells is achieved in an in vitro culture system. A sac-like structure encloses hematopoietic progenitor cells, which is obtained by inoculating iPS cells onto feeder cells and then culturing the iPS cells under conditions suitable for inducing the differentiation of hematopoietic progenitor cells. Moreover, a method for producing various types of blood cells, comprises culturing hematopoietic progenitor cells enclosed in the sac-like structure under conditions suitable for inducing the differentiation of blood cells. Furthermore, a method for producing various types of blood cells, particularly megakaryocytes and platelets, is achieved without involving the sac-like structure.

An object of the present invention is to provide a sac-like structure enclosing hematopoietic progenitor cells and a method for preparing the sac-like structure as well as a method for efficiently preparing blood cells such as mature megakaryocytes and platelets from the sac-like structure. The present invention provides a sac-like structure enclosing hematopoietic progenitor cells, the sac-like structure being obtained by plating ES cells onto feeder cells and culturing the ES cells under suitable conditions for inducing hematopoietic progenitor cell differentiation. Moreover, the present invention provides a method for producing various blood cells, the method comprising further culturing hematopoietic progenitor cells enclosed in the sac-like structure under suitable conditions for inducing blood cell differentiation.

There is described herein a method of enriching a population of stem cells for hematopoietic progenitors. The method comprises inducing hematopoietic differentiation in a population of human embryonic stem cells or human induced pluripotent stem cells; sorting the population based on expression of CD43 and at least one of CD34, CD31 and CD144; and selecting a fraction that is at least one of CD34+CD43−, CD31+CD43− and CD144+CD43−. Also provided are populations of hematopoietic progenitors obtained by the methods described herein.

Recombinant lentiviral vectors having a region encoding a functional β-globin gene; and large portions of the β-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of β-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including β-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than untransformed cells allows selection by treatment of the cells with the corresponding drug.

An object of the present invention is to expand CD34+ cells ex vivo efficiently in a short term using a biologically safe and inexpensively obtainable low molecular weight compound. A still another object of the present invention is to provide an expansion agent for CD34+ cells useful for treatment of various hematopoietic disorders caused by dysfunctional hematopoietic stem cells and / or hematopoietic progenitor cells.A method for expanding CD34+ cells, which comprises culturing CD34+ cells ex vivo in the presence of a compound represented by the formula (I) (wherein A, B, L1, L2, L3, L4, R1, R2, R3, X and Y are defined in the description), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof.

The invention discloses a serum-free culture medium for hematopoietic stem cell in vitro expansion culture and a preparation method thereof. The culture medium for in vitro expansion of the hematopoietic stem cell is free from introducing exogenous gene expression, and the genome stability of the original stem cell is unchanged, the tumorigenic risk is avoided, and the stem cell transplantation safety problem caused by feeder layer cell and other exogenous cell mixing is not involved; through the combined application of various cytokines, a proper culture condition and properexpansion time are selected to overcome the defect that the expansion number is insufficient, the number is effectively expanded, and the quality is maintained at the same time, namely, the effect of maintaining hematopoietic reconstitution capacity through the expansion of the early hematopoietic progenitor cell and reservation of the HSC is achieved.

The invention discloses a method for preparing human hematopoietic stem cells by using human hematopoietic progenitor cells, comprising the following steps: S1 preparing CD34+CD90- and CD34+CD45RA+ umbilical cord hematopoietic progenitor cells from human umbilical cord blood; S2) suspending the CD34+CD90- and CD34+CD45RA+ umbilical cord hematopoietic progenitor cells in a medium specially used forumbilical cord hematopoietic stem cells transformation and culturing the cells, the medium adopting a StemSpan SFEM II serum-free culture medium and 100ng / ml SCF, 100ng / ml FLT3 and 50ng / ml TPO beingadded into the medium, wherein the cell seeding density in 24-well plate is 0.55 *10<4> cells / well for CD34+CD90-cells, and 0.13 *10<4> cells / well CD34+CD45RA+ cells; 1[mu]M of MS-275 is added, and culture is performed at 37 DEG C in an incubator with the CO2 concnetration being 5%. The method has the beneficial effects that the hematopoietic stem cells prepared by using the human hematopoietic progenitor cells are high in quantity and have the differentiation potential of each lineage, and can provide a hematopoietic stem cell donor for clinical application.

Flt3-ligand can be used to generate large numbers of dendritic cells from hematopoietic progenitor and stem cells. Flt3-ligand can be used to augment immune responses in vivo, and expand dendritic cells ex vivo. Such dendritic cells can then be used to present tumor, viral or other antigens to naive T cells, can be useful as vaccine adjuvants. When flt3-L is used and / or administered in combination with other reactive agents, e.g. CD40 binding proteins, 4-1BBL or antibodies reactive with 4-1BB, CD30 ligand antagonists, RANKL, and / or interferon alpha the combination further enhances immune responses and the effectiveness of vaccine adjuvants.

Flt3-ligand can be used to generate large numbers of dendritic cells from hematopoietic progenitor and stem cells. Flt3-ligand can be used to augment immune responses in vivo, and expand dendritic cells ex vivo. Such dendritic cells can then be used to present tumor, viral or other antigens to naive T cells, can be useful as vaccine adjuvants. When flt3-L is used and / or administered in combination with other reactive agents, e.g. CD40 binding proteins and 4-1BBL or antibodies reactive with 4-1BB, the combination further enhances immune responses and the effectiveness of vaccine adjuvants.

A method for producing CD4 / CD8 double-positive T cells including the following steps: (1) a step that cultures pluripotent stem cells in culture fluid and induces hematopoietic progenitor cells and (2) a step that cultures the hematopoietic progenitor cells obtained in step (1) in culture fluid containing a p38 inhibitor and / or SDF-1 and induces CD4 / CD8 double-positive T cells.

The invention is in the area of pleuripotent stem cells generated from adipose tissue-derived stromal cells and uses thereof. In particular, the invention includes isolated adipose tissue derived stromal cells that have been induced to express at least one phenotypic characteristic of a neuronal, astroglial, hematopoietic progenitor, or hepatic cell. The invention also includes an isolated adipocyte tissue-derived stromal cell that has been dedifferentiated such that there is an absence of adipocyte phenotypic markers.