Abstract: Provided are: a method for producing an immortalized human erythroid progenitor cell line, enabling efficient and stable production of enucleated red blood cells; and a method for producing human enucleated red blood cells from a human erythroid progenitor cell line obtained by the aforementioned production method. An expression cassette capable of inducing expression of HPV-E6/E7 genes in the presence of DOX was introduced into the genomic DNA of blood stem cells. Then, the blood stem cells were cultured in the presence of DOX and a blood growth factor. Thereby, immortalized cell lines of human erythroid progenitor cells were established. Further, it was revealed that culturing the cell lines under a condition where the expression of the HPV-E6/E7 genes was not induced enabled differentiation induction into enucleated red blood cells at a high ratio.

Abstract: Methods of efficiently converting primate pluripotent stem cells to GABA neurons or cholinergic neurons, as well as applications thereof, are disclosed.

Abstract: A method for efficient generation of neutrophils, eosinophils, macrophages, osteoclasts, dendritic cells an Langerhans cells from human embryonic stem cells is disclosed.

Abstract: A spermatogonial stem cell line that is derived from testes of rats characterized by a desirable genetic background can serve as a source for cells to transplant into male-sterile recipient animals that are immuno-compatible with the spermatogonial line. Rat cells thus transplanted readily develop into fertilization-competent, haploid male gametes, with little or no endogenous sperm competition generated by the testes of the male-sterile recipient. This approach, constituting the first vector system for the use of rat spermatogonial lines from in vitro culture in generating mutant rats on a desired genetic background, effects maximal germline transmission of donor haplotypes from the transplanted spermatogonial cells.

Abstract: The invention provides, among other things, methods and systems for expanding CD133+ cells. The invention further provides methods and systems for increasing the blood flow to an ischemic tissue in a subject in need thereof, such as to ischemic myocardium. The invention further provides methods and systems for directing differentiation of expanded CD133+ cells. The invention further provides methods and systems for treating a subject with differentiated cells in a subject in need thereof.

Abstract: Provided herein are methods of producing erythrocytes from hematopoietic cells, particularly hematopoietic cells from placental perfusate in combination with hematopoietic cells from umbilical cord blood, wherein the method results in accelerated expansion and differentiation of the hematopoietic cells to more efficiently produce administrable erythrocytes. Further provided herein is a bioreactor in which hematopoietic cell expansion and differentiation takes place.

Abstract: An in vitro or ex vivo method of producing a population of lineage committed haematopoietic progenitor or mature haematopoietic cells other than cells of the neutrophil lineage, including the steps of providing a population of haematopoietic progenitor cells; and culturing the haematopoietic progenitor cells in an animal cell culture medium including one or more cytokines that differentiate the haematopoietic progenitor cells into lineage committed haematopoietic progenitor and/or mature haematopoietic cells, under static conditions until the cells are at a cell density at which oxygen transfer via the surface of the culture medium is insufficient for growth of the progenitor cells and progeny thereof under static conditions, and then agitating the culture medium to produce a population of lineage committed haematopoietic progenitor or mature haematopoietic cells other than cells of the neutrophil lineage.

Abstract: This invention relates to the culture of dendritic cells from human embryonic stem (ES) cells. Human ES cells are first cultured into hematopoietic cells by co-culture with stromal cells. The cells now differentiated into the hematopoietic lineage are then cultured with GM-CSF to create a culture of myeloid precursor cells. Culture of the myeloid precursor cells with the cytokines GM-CSF and IL-4 causes functional dendritic cells to be generated. The dendritic cells have a unique phenotype, as indicated by their combination of cell surface markers.

Abstract: RP-factors, their cognate receptors, convertases, respective genes and inhibitors or mimetics thereof are described. In particular, antibodies, pharmaceutical compositions and (therapeutic, diagnostic) methods based on the RP-factors and their receptors/convertases are described.

Abstract: A cell culture chamber and a cell culture method that are capable of effectively constructing an intercellular network in a culture space are provided. A cell culture chamber (10)according to the present invention is a cell culture chamber (10)including a plurality of microchambers (11) formed on a surface thereof, characterized in that convex portions (side walls 12) that partition the microchambers (11) adjacent to each other are formed to prevent cells from being adhered to upper surfaces of the convex portions. Consequently, cells can be cultured exclusively within the microchambers (11), and an intercellular network can be constructed effectively.

Abstract: A method for inducing differentiation of ES cells into cardiomyocytes, which comprises contacting the ES cells with an agonist for G-CSF receptor.

Abstract: Disclosed are cells, methods of modulating cells, and therapeutic uses of the cells for the immune modulation of mammals in need thereof. Immune modulation including alteration of cytokine profile, cytotoxic activity, antibody production and inflammatory states is achieved through the administration of various cell types that have been unmanipulated or manipulated in order to endow specific biological activity. Cellular subsets and administration of the subsets in combination with various agents are also provided. One embodiment teaches the previously unknown finding that adipose tissue derived mononuclear cells contain T cells with immune regulatory properties that alone or synergistically with various stem cells induce immune modulation upon administration. Another embodiment is the finding that stimulation of stem cell activation results in stem cell secondary activation of immune modulatory cells, one type which is T regulatory cells (Tregs).

Abstract: A method of ex-vivo expanding a population of stem cells, while at the same time inhibiting differentiation of the stem cells. The method comprises ex-vivo providing the stem cells with conditions for cell proliferation and with at least one copper chelator in an amount and for a time period for permitting the stem cells to proliferate and, at the same time, for reducing a capacity of the stem cells to differentiate.

Abstract: The invention relates to methods for preparing and performing quantitative PCR analyses, a new sealing device and a new use. According to the invention, a sample vessel containing the samples to be analyzed is sealed by placing a planar sealing device on the vessel to cover the samples and applying pressure on the sealing device in order to deform the sealing device so as to form a light-refracting geometry individually for the samples to be analyzed. The invention offers a convenient way of sealing the vessel and forming analysis-improving optical lenses over the samples simultaneously.

Abstract: A method is provided for producing a population of post-mitotic cells of the neutrophil lineage, which method comprises the ex vivo steps of: (a) providing a population of cells comprising neutrophil progenitor cells; and (b) culturing the population of cells in an animal cell culture medium comprising (i) one or more early acting cytokines and (ii) one or more cytokines that differentiate said progenitor cells into a neutrophil specific lineage, under conditions of low oxidative stress, the culture medium being agitated when the cells are at a cell density at which oxygen transfer via the surface of the culture medium is insufficient for growth of the progenitor cells and the progeny thereof under static conditions, to produce a population of post-mitotic cells of the neutrophil lineage. The resulting population of cells can be used to increase the number of neutrophils in a patient.

Abstract: This invention relates to the culture of dendritic cells from human embryonic stem (ES) cells. Human ES cells are first cultured into hematopoietic cells by co-culture with stromal cells. The cells now differentiated into the hematopoietic lineage are then cultured with GM-CSF to create a culture of myeloid precursor cells. Culture of the myeloid precursor cells with the cytokines GM-CSF and IL-4 causes functional dendritic cells to be generated. The dendritic cells have a unique phenotype, as indicated by their combination of cell surface markers.

Abstract: Methods for the diagnosis of visceral, cutaneous and canine leishmaniasis in a subject suspected of being infected with the parasitic protozoa Leishmania is disclosed. Disclosed are antibody-capture enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies to Leishmania parasite soluble antigens and antigen-capture ELISAs for the detection of Leishmania parasite soluble antigens in host samples. Also disclosed are immunodiagnostic kits for the detection of Leishmania parasite circulating antigens or IgM and IgG antibodies in a sample from subject having visceral, cutaneous or canine leishmaniasis. In these methods and kits, detection may be done photometrically or visually. The methods and kits also allow the visualization of Leishmania amastigotes or promastigotes in a sample.

Abstract: A system combining a clonogenic differentiation assay with an instrument-based ATP bioluminescence proliferation assay to produce a standardized colony-forming stem and progenitor cell potency assay is provided.

Abstract: A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.

Abstract: The present invention relates generally to kits that provide reagent mixes and instructions for the use thereof, in performing high-throughput assay methods that determine the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells. The present invention further relates to kits that provide reagent mixes and instructions for high-throughput assays methods for screening compounds that may modulate the proliferative status of a target cell population. The kits of the present invention and methods therein described may be used for determining the proliferative status of any isolated cell line or type. The kits and methods of the present invention address the need for rapid assays that determine the proliferative status of isolated hematopoietic stem and progenitor cells and of subpopulations of differentiated cells thereof.

Abstract: The disclosure provides methods of modulating the activity of DDR1. Methods for screening for agents that activate DDR1 are disclosed. Methods for inducing the maturation of immature macrophages and immature dendritic cells are also disclosed. In addition, methods for increasing neutrophil activation using a DDR1 activating agent, and methods for increasing leukocyte migration using a DDR1 activating agent, are provided.

Abstract: Provided are mutant class III receptor tyrosine kinases (RTKIII) comprising a mutation at the amino acid residue corresponding to the conserved cysteine at residue 432 (C432) or 439 (C439) of a mouse colony-stimulating factor (1) receptor (CSF-IR) precursor having the amino acid sequence of SEQ ID NO: 1, where the mutation is a replacement of the cysteine with an amino acid having an uncharged polar R group. Also provided are mutant RTKIIIs comprising a tyrosine to phenylalanine mutation. Additionally provided are extracellular domains of the above-identified mutant RTKIIIs comprising cysteine to serine mutations. Further provided are stable cell lines of macrophages lacking a native CSF-IR. Also provided are isolated nucleic acids encoding any of the above-described mutant RTKIIIs or extracellular domains. Vectors comprising those nucleic acids are also provided. Additionally provided are methods of preparing the above-identified stable cell lines.

Abstract: This invention relates to the culture of dendritic cells from human embryonic stem (ES) cells. Human ES cells are first cultured into hematopoietic cells by co-culture with stromal cells. The cells now differentiated into the hematopoietic lineage are then cultured with GM-CSF to create a culture of myeloid precursor cells. Culture of the myeloid precursor cells with the cytokines GM-CSF and IL-4 causes functional dendritic cells to be generated. The dendritic cells have a unique phenotype, as indicated by their combination of cell surface markers.

Abstract: The present invention relates generally to high-throughput assay methods that determine the proliferative status of hematopoietic stem and progenitor cells. The present invention further relates to high-throughput assays for screening compounds that modulate the growth of hematopoietic stem and progenitor cells and for identifying subpopulations thereof that are suitable for transplantation. The assay of the present invention is particularly useful for quality control and monitoring of the growth potential in the stem cell transplant setting and would provide improved control over the reconstitution phase of transplanted cells.

Abstract: This invention relates to methods of producing oligodendrocytes from multipotent neural stem cells by using at least one oligodendrocyte promoting factor, particularly granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 3 or interleukin 5. The neural stem cells may optionally be expanded prior to being subjected to the oligodendrocyte promoting factor.

Abstract: The present invention relates generally to high-throughput assay methods that determine the proliferative status of hematopoietic stem and progenitor cells. The present invention further relates to high-throughput assays for screening compounds that modulate the growth of hematopoietic stem and progenitor cells and for identifying subpopulations thereof that are suitable for transplantation. The assay of the present invention is particularly useful for quality control and monitoring of the growth potential in the stem cell transplant setting and would provide improved control over the reconstitution phase of transplanted cells.

Abstract: Methods are provided for enhancing viability comprising administering at least one inhibitor of p53 or a p53-associated pathway to one or more of the following: the embryo, oocytes, sperm, a femme animal or a male animal.

Abstract: The present invention relates generally to assays, methods, and kits that provide reagent mixes and instructions for determining the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells.

Abstract: Disclosed and claimed are methods for the isolation and use of stem cell inhibiting factors for regulating the abnormal stem cell cycle and for accelerating the post-chemotherapy peripheral blood cell recovery. Also disclosed and claimed are the inhibitors of stem cell proliferation.

Abstract: We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or “priming” phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or “differentiation” phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.

Abstract: The present invention provides an apparatus for stimulating an animal cell and recording its physiological signal and methods of making and using thereof. The purpose of the present invention is to provide an apparatus for stimulating an animal cell and recording its physiological signal that is efficient, convenient, and accurate. The apparatus for stimulating an animal cell and recording its physiological signal of the present invention comprises a poor conductive substrate, wherein on at least one surface of the substrate is provided at least one unit conductive polymer layer and at least one good conductive microelectrode.

Abstract: Methods for the diagnosis of visceral, cutaneous and canine leishmaniasis in a subject suspected of being infected with the parasitic protozoa Leishmania is disclosed. Disclosed are antibody-capture enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies to Leishmania parasite soluble antigens and antigen-capture ELISAs for the detection of Leishmania parasite soluble antigens in host samples. Also disclosed are immunodiagnostic kits for the detection of Leishmania parasite circulating antigens or IgM and IgG antibodies in a sample from subject having visceral, cutaneous or canine leishmaniasis. In these methods and kits, detection may be done photometrically or visually. The methods and kits also allow the visualization of Leishmania amastigotes or promastigotes in a sample.

Abstract: The present invention relates to a process for deriving dendritic cells from mononuclear cells in culture comprising the step of putting in contact type I IFN with said mononuclear cells. Dendritic cells suitable as cellular adjuvants in prophylactic as well as therapeutic vaccination of animal and human beings, are obtainable thereby, after a single step treatment in a brief period of time. Dendritic cells obtainable thereby, pharmaceutical compositions including them, in particular a vaccine comprising said cells as active principle, and a method of treatment of a pathology associated with the presence of an antigen in human beings, are further objects of the invention, as well as a kit for deriving said dendritic cells and a method for the ex vivo expansion of T cells using them.

Abstract: A method of inducing dendritic cell (DC) development by administering Macrophage-Colony Stimulating Factor Receptor Ligand is provided. M-CSF receptor ligands induce DCs to differentiate into subtypes, for example plasmacytoid DCs and conventional DCs. Induction with an M-CSF receptor ligand can be achieved in vitro from hematopoietic precursors, such as bone marrow cells, or in vivo. In vitro, M-CSF receptor ligand-derived DCs can be used to produce cytokines and to stimulate other immune response cells. M-CSF receptor ligands can also be used to induce precursor cells removed from an animal to develop into DCs. In addition, these isolated DCs can be exposed to antigens to stimulate a specific immune response when reintroduced into the animal. Treatments for cancers, such as Acute Myeloid Leukemia, and autoimmune diseases such as Systemic Lupus Erythematosus, are also provided in the invention.

Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.

Abstract: This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of mouse embryonic fibroblast feeder cells to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by defined components added to the culture environment that support rapid proliferation without differentiation. The medium contains an isotonic buffer, a blend of essential nutrients such as protein and lipids, and an effective growth factor or combination of factors that promote proliferation while inhibiting differentiation. Culturing human embryonic stem cells in fresh medium on an extracellular matrix according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers.

Abstract: The present invention concerns the field of biology and virology. In particular, the invention concerns a method for obtaining human cell lines, in particular human stem cells derived from human embryonic stem cells, the method comprising separation from the serum, the feeder layer and at least one growth factor. The cell lines are capable of proliferating indefinitely in a basic culture medium. The invention also concerns the use of the cells derived from such cell lines for virus replication, and more particularly for producing human or veterinary vaccines, as well as for producing recombinant proteins of therapeutic interest.

Abstract: A method of scoring the biological activity of bioactive agents like colostrum comprising conducting separate bioassays for cell restitution and cell proliferation on the bioactive agent, a comparative growth factor stimulating agent, and (preferably) a negative baseline control sample containing the cells and growth medium alone. These values are then plugged into the equations provided in this application to calculate a Restitution Score (“RS”), Proliferation Score (“PS”), and a composite repair and protection factor score (“RPF”). In this manner, the bioactivity of compositions that enhance the repair and/or proliferation of mammalian cells, or act as additives to growth media used to maintain and grow laboratory cell cultures can be quickly and reproducibly obtained. This invention may be applied to a wide variety of bioactive agents used to treat a large assortment of functional cells in organ tissues.

Abstract: The invention relates to a method for reducing glucose consumption during cultivation of animal cells, which comprises cultivating animal cells in the presence of a bi- or tricarbonic acid or a salt thereof at a concentration of about 1 to 50 mmol/l.

Abstract: The present invention relates to novel immortalized precursor cell populations derived from embryonic stem cell populations and methods to produce such cell populations. Also disclosed is an assay to identify regulatory compounds capable of controlling cell growth for therapeutic and experimental use.

Abstract: The present invention relates generally to high-throughput assay methods that determine the proliferative status of hematopoietic stem and progenitor cells. The present invention further relates to high-throughput assays for screening compounds that modulate the growth of hematopoietic stem and progenitor cells and for identifying subpopulations thereof that are suitable for transplantation. The assay of the present invention is particularly useful for quality control and monitoring of the growth potential in the stem cell transplant setting and would provide improved control over the reconstitution phase of transplanted cells.

Abstract: The present invention relates generally to kits that provide reagent mixes and instructions for the use thereof, in performing high-throughput assay methods that determine the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells. The present invention further relates to kits that provide reagent mixes and instructions for high-throughput assays methods for screening compounds that may modulate the proliferative status of a target cell population. The kits of the present invention and methods therein described may be used for determining the proliferative status of any isolated cell line or type. The kits and methods of the present invention address the need for rapid assays that determine the proliferative status of isolated hematopoietic stem and progenitor cells and of subpopulations of differentiated cells thereof.

Abstract: We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or “priming” phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or “differentiation” phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.

Abstract: A method of ex-vivo expanding a population of stem cells, while at the same time inhibiting differentiation of the stem cells.

Abstract: The present invention provides cultured leukemia cells. The method comprises isolating mononuclear cells, which contain leukemia cells, culturing the leukemia cells in a chamber having a scaffolding covered or surrounded with culture medium, where the scaffolding allows for leukemia cells to have cell to cell contacts in three dimensions. The subject leukemia cells are useful for screening compounds which inhibit or stimulate leukemia cell function or formation.

Abstract: The invention relates to a method for activating human-derived antigen-presenting cells by in vitro cultivation with at least one of the glycoside compounds represented by formula (A) or salts thereof [preferred example: (2S,3S,4R)-1-(?-D-galactopyranosyloxy)-2-hexacosanoylamino-3,4-octadecanediol], and to human antigen-presenting cells activated by the method. The invention also relates to a method for treatment of cancer and infectious diseases including AIDS with the activated human antigen-presenting cells, and to a use of the activated human antigen-presenting cells in the preparation of medicines for treating such diseases. The invention can provide a satisfactory therapeutic effect on cancer and infectious diseases including AIDS without the need to pulse the human antigen-presenting cells with tumor antigens.

Abstract: The present invention relates to immortalized, malignant, human, adult prostate epithelial cell lines or cell lines derived therefrom useful in the diagnosis and treatment of prostate cancer. More particularly, the present invention relates to cloned, immortalized, malignant, human, adult prostate epithelial cell lines and uses of these cell lines for the diagnosis and treatment of cancer. Furthermore, the present invention provides for the characterization of said cell lines through the analysis of specific chromosomal deletions.

Abstract: The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+and CD8+T cells.

Abstract: The present invention relates to a substantially pure population of viable pancreatic progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Abstract: Ligands for flt3 receptors capable of transducing self-renewal signals to regulate the growth, proliferation or differentiation of progenitor cells and stem cells are disclosed. The invention is directed to flt3-L as an isolated protein, the DNA encoding the flt3-L, host cells transfected with cDNAs encoding flt3-L, compositions comprising flt3-L, methods of improving gene transfer to a mammal using flt3-L, and methods of improving transplantations using flt3-L. Flt3 -L finds use in treating patients with anemia, AIDS and various cancers.