Abstract: 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.

Abstract: An in vitro human cardiac multi potent or unipotent cell that has the ability to proliferate; may be maintained in standard cardiac stem cell media; can differentiate to a progenitor, precursor, or somatic cell; has the characteristics of a cardiac stem cell, a cardiac precursor cell, or a cardiac progenitor cell; does not exhibit uncontrolled growth, teratoma formation, or tumor formation in vivo; expresses one or more markers of a multipotent, unipotent or somatic cell not characteristic of a cardiac stem cell, a cardiac precursor cell, or a cardiac progenitor cell; and is derived from the reprogramming of a somatic cell, a progenitor cell or a stem cell that exhibits at least a transient increase in intracellular levels of at least one reprogramming agent; wherein the cell comprises at least one transiently expressed polypeptide or an expression vector.

Abstract: The present invention provides compositions and methods for transforming primary mammalian cells using an oncogenic form of ALK wherein the transformed cells display features of that of a corresponding tumor cell isolated from a cancer subject. The invention also provides a method for immortalizing normal CD4+ T lymphocytes with a lymphoma-characteristic form of ALK such as NPM-ALK.

Abstract: The present invention relates to immortalized avian cell lines suitable for production of biologicals or viruses for vaccination. In particular, the cell lines are derived from primary cells which are transformed with at least two viral or cellular genes, one of which causes cell cycle progression whereas the other interferes with innate protective mechanisms of the cell induced by dysregulated replication. The invention moreover relates to the production of said immortalized cell lines and their use for producing biologicals or viruses for vaccination.

Abstract: The present invention relates to a method for the production of a permanent human cell line, wherein isolated primary human cells are transfected simultaneously with a sequence allowing the expression of at least one cell transforming factor and a sequence allowing the expression of at least one recombinant polypeptide.

Abstract: A method of generating an induced progenitor population (iPP) of cells and/or induced population of cells from somatic cells, comprising the steps: a) obtaining a starting cell population, wherein cells of the starting cell population comprise, or are contacted with, a nucleic acid molecule encoding four reprogramming factors under the control of a control element, wherein the four reprogramming factors are optionally Oct4, Klf4, Sox2 and c-Myc, and wherein the control element prevents or stops expression of the reprogramming factors under its control in the absence of induction by an inducing agent; and b) transiently inducing expression of the reprogramming factors in the starting cell population to obtain an iPP, c) optionally isolating the iPP, and d) terminating the transient induction while the proliferative capacity of the iPP remains under the control of the one or more exogenous reprogramming factors to produce an induced population of cells.

Abstract: Disclosed are methods for conditionally immortalizing stem cells, including adult and embryonic stem cells, the cells produced by such methods, therapeutic and laboratory or research methods of using such cells, and methods to identify compounds related to cell differentiation and development or to treat diseases, using such cells. A mouse model of acute myeloid leukemia (AML) and cells and methods related to such mouse model are also described.

Abstract: The present invention relates to an improved method for the serum-free production of an immortalized human cell line stably transfected under serum-free conditions with a specific vector carrying the gene coding for the protein of interest. Furthermore the invention relates to a production cell line obtained by said method, a production method for said protein of interest utilizing said production cell line, and the specific vector carrying the gene of interest itself.

Abstract: Disclosed herein is the finding that Zscan4 is an early embryonic factor that facilitates cellular reprogramming. In particular, Zscan4 can replace the oncogenic reprogramming factor c-Myc to produce induced pluripotent stem cells when co-expressed with Klf4, Oct4 and Sox2. In addition, several Zscan4-dependent genes were identified that promote iPSC formation when co-expressed with known reprogramming factors. Thus, the present disclosure provides an ex vivo method of producing an iPS cell by reprogramming of a somatic cell. The method includes contacting the somatic cell with a Zscan4, or a Zscan4-dependent gene, and at least one reprogramming factor. Also provided are iPS cells produced by the disclosed method and non-human animals generated from such iPS cells.

Abstract: Presented herein are methods of generating an induced stem cell (iSC) from a somatic cell, by contacting the somatic cell with an induction factor that reprograms the somatic cell to generate an iSC. The induction factor can be a genetic construct or a fusion protein. Where the induction factor is a genetic construct, the construct bears one or more nucleotide sequences encoding one or more reprogramming elements selected from OCT4, SOX2, NANOG, and a Notch pathway molecule, or an active fragment or derivative thereof. The genetic construct can have a lentiviral or episomal vector backbone. The induction factor can also be a fusion protein, with the reprogramming element being a protein selected from OCT4, SOX2, NANOG, or a Notch pathway molecule, or an active fragment or derivative thereof. The fusion protein can be TAT protein or an active fragment or derivative thereof.

Abstract: Described herein is a gene regulatory network based focused approach to cell transformation. The methods described herein allow for identification of circuit and sub-circuit repertoires for which modification in a starting cell type can result in generation of a transformed cell type in a durable and persistent manner, without requiring potentially deleterious genome modification. The described methods and compositions produced by the methods find widespread application in regenerative medicine applications.

Abstract: Described herein are methods and related compositions for inducing differentiation of human pluripotent stem cells (hPSCs) into hemogenic endothelium with pan-myeloid potential or restricted potential, by forced expression in the hPSCs of a combination of transcription factors as described herein.

Abstract: Methods and compositions relating to the production of induced pluripotent stem cells (iPS cells) are disclosed. For example, induced pluripotent stem cells may be generated from peripheral blood cells, such as human blood progenitor cells, using episomal reprogramming and feeder-free or xeno-free conditions. In certain embodiments, the invention provides novel methods for improving overall reprogramming efficiency with low number of blood progenitor cells.

Abstract: Establishment of human pluripotent stem cells having properties close to human ES cells with the genome of the patient per se that can circumvent immunological rejection of transplanted cells from cells derived from a postnatal human tissue are described. Human pluripotent stem cells can be induced by introducing three genes of Oct3/4, Sox2 and Klf 4, or three genes of Oct3/4, Sox2 and Klf 4 plus the c-Myc gene or a histone deacetylase (HDAC) inhibitor of undifferentiated stem cells present in various human postnatal tissues in which each gene of Tert, Nanog, Oct3/4 and Sox2 has not undergone epigenetic inactivation.

Abstract: A transgene for endowing human quiescent cells from primary cultures with exogenously inducible telomere length homeostasis and cell cycle traverse is described. The transgene includes at least three promoter sequences; a G1-specific RNA interference sequence which is operably linked downstream of a first promoter sequence; a telomere length maintenance gene sequence which is operably linked downstream to a second promoter sequence; a Scaffold/Matrix attachment region (S/MAR) element positioned downstream in frame with said telomere length maintenance gene sequence and an exogenously-inducible transcriptional regulation system. The transgene is useful to immortalize human quiescent cells from primary cultures.

Abstract: Systems, constructs, and methods for reprogramming cells are provided. In one aspect, for example, a transformation construct for generating iPS cells can include an expression vector having a plurality of reprogramming factors, each reprogramming factor being under control of a separate promoter.

Abstract: Provided herein are, inter alia, methods of generating vascular progenitor cells from primary cells without reprogramming the primary cell into a pluripotent stem cell. The vascular progenitors provided herein may be used to form endothelial cells or smooth muscle cells. Further provided are isolated mutlitpotent cells useful to form vascular progenitor cells.

Abstract: An object of the present invention is to provide a method of promoting polyploidization of megakaryocytes and thereby producing highly polyploidized megakaryocytes, a method of efficiently producing platelets from polyploidized megakaryocytes, and the like. The present invention provides a method of producing polyploidized megakaryocytes comprising a step of forcing expression of an apoptosis suppressor gene in megakaryocytes before polyploidization and culturing the resulting cells.

Abstract: A gene complex for reversibly immortalizing cells contains an immortalizing gene region, which possesses at least a resistance gene, an immortalizing gene and, preferably, a suicide gene, and also two sequences which flank the gene region and which function as recognition sites for homologous intramolecular recombination, and at least one promoter located upstream of the gene region. A gene complex for imnomodulating cells contains a first immunomodulating gene region, whose expression inhibits the function of MHC I molecules, a second immunomodulating gene region, whose expression leads to the inactivation of natural killer cells, and a resistance gene. A method for obtaining cells involves preparing organ-related cells which are immortalized by transferring the first gene complex and immunomodulated by transferring the second gene complex. After the immortalized cells have been expanded, the immortalization is reversed.

Abstract: The invention relates to a method for reprogramming cells from aged donors or senescent cells to pluripotent cells that have lost marks of senescence. In particular, the invention relates to an ex vivo method for preparing induced pluripotent stem cells (iPSCs) from a target cell population comprising cells from aged donors or senescent cells, said method comprising the steps of culturing said target cell population under appropriate conditions for reprogramming said cells into iPSCs, wherein said appropriate conditions comprises increasing expression in said target cells, of at least the following reprogramming factors: Oct4, Klf4, Sox2, c-Myc, Lin28 and, optionally Nanog.

Abstract: This application relates to a method for converting somatic cells to Neural Stem Cells (NSCs). Moreover this application relates to a method for converting human fibroblasts, keratinocytes or adipocytes to neural stem cells based on linked steps of genes transduction and chemically defined medium induction.

Abstract: Methods and composition of induction of pluripotent stem cells and other desired cell types are disclosed. For example, in certain aspects methods for generating essentially vector-free induced pluripotent stem cells are described. Furthermore, the invention provides induced pluripotent stem cells and desired cell types essentially free of exogenous vector elements with the episomal expression vectors to express differentiation programming factors.

Abstract: Disclosed is a cell which enables the reproduction of a cartilage tissue and has a proliferative ability. Also disclosed is a technique for providing a cell supply source which can be used in a definitive treatment of osteochondrosis deformans. A chondrocyte-like cell which has the same properties as those of a chondrocyte and can proliferate can be produced by selecting a combination of an Myc family gene and/or a Klf family gene and a SOX9 gene and introducing the combination into a somatic cell. The chondrocyte-like cell can be used for a medical purpose of cartilage regeneration.

Abstract: Methods and compositions for transdifferentiation of an animal cell from (i) a first pluripotent cell fate to a second nonpluripotent cell fate or (ii) from a non-pluripotent mesodermal, endodermal, or ectodermal cell fate to a different non-pluripotent mesodermal, endodermal, or ectodermal cell fate.

Abstract: The present invention provides for identification and use of small molecules to induce pluripotency in mammalian cells as well as other methods of inducing pluripotency.

Abstract: The invention provides a method of improving the efficiency of establishment of induced pluripotent stem cells by increasing, in a nuclear reprogramming step of somatic cell, the level of activated form of one or more proteins selected from the group consisting of Ras family members, PI3 kinase, RalGEF, Raf, AKT family members, Rheb, TCL1 and S6K. The invention also provides a method of producing induced pluripotent stem cells by contacting a somatic cell with a nuclear reprogramming substance and one or more of such proteins and nucleic acids that encode such proteins. The invention further provides an induced pluripotent stem cell that has an exogenous nucleic acid encoding such a protein, as well as agents for use in the aforesaid methods.

Abstract: This invention relates to immortalized avian cells, and to the use of these cells for the production of viruses. The cells according to the invention are particularly useful for the production of recombinant viral vectors which can be used for the preparation of therapeutic and/or prophylactic compositions for the treatment of animals and more particularly humans.

Abstract: A method for modulating cell differentiation capabilities using heterologous gene expression. Some embodiments of the invention relate to a method for inducing a cardiac progenitor cell by delivering a reprogramming factor to the cell, wherein the reprogramming factor comprises ETS2 or a combination of ETS2 and Mesp1.

Abstract: The present invention relates to methods of producing a reversibly immortalized cell, cells obtainable by the above method, eukaryotic cells comprising one or more nucleic acid(s) coding for one or more immortalizing protein(s) and methods of re-differentiating these cells.

Abstract: Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.

Abstract: A method for preparing neoplastically transformed cells from human-derived cells, including the step of introducing human telomerase catalytic subunit (hTERT) gene, SV40 small T antigen (SV40ST) gene, and an antisense oligonucleotide derived from human 28S rRNA into the human-derived cells. The method for preparing neoplastically transformed cells from human-derived cells can be utilized when a variety of human normal cells are induced to be neoplastically transformed in order to elucidate cancer onset mechanisms, so that the method can be effectively utilized in search of target molecules for a new medicament.

Abstract: An object of the present invention is to provide a method for producing tumor cells from cells derived from normal cells without using hTERT. The present invention provides a method for producing tumor cells by carrying out the following treatments (1) and (2) on normal mammary epithelial cells: (1) elimination of p53 function; and (2) introduction v-Src gene.

Abstract: The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. The invention also provides methods to transform normal primary cells so cultured into “cancer stem cells.” The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.

Abstract: The present invention relates, in general, to human B cells, and, in particular to a method of immortalizing and cloning human B cells and to monoclonal antibodies derived therefrom. The invention further relates to methods of using the monoclonal antibodies for therapeutic and diagnostic purposes.

Abstract: The present invention provides a methodology that can develop a more excellent anti-cancer drug than conventional ones for various cancers. Specifically, the present invention provides a method for establishing an artificial cell, comprising treating a cancer cell with an expression vector for a foreign oncogene and then culturing the cancer cell treated with the expression vector under a condition which inhibits an expression or function of an oncogene that is inherent to the cancer cell, and an established artificial cell; a method of screening an anti-cancer drug, comprising evaluating whether or not a test substance inhibits a proliferation of the artificial cell; as well as a method for identifying an oncogene, comprising treating a cancer cell with an expression vector for a test gene and then culturing the cancer cell treated with the expression vector under a condition which inhibits an expression or function of an oncogene that is inherent to the cancer cell.

Abstract: The present invention has an object of providing a method for producing specific cells by amplifying cells in a desired differentiation stage. The present invention provides a method for producing specific cells by inducing differentiation of cells, wherein an oncogene is forcibly expressed in cells in a desired differentiation stage to amplify the cells in the desired differentiation stage. The present invention also provides a method for producing specific cells, wherein oncogene-induced senescence (OIS) which is induced by the oncogene expressed in the cells in the desired differentiation stage is suppressed.

Abstract: We describe a method of monitoring the state of a cell, the method comprising establishing, for a selected microRNA (miRNA) species secreted by the cell, a ratio of: (a) a precursor form of the miRNA species (pre-miRNA); to (b) a mature form of the miRNA species (mature miRNA); in which the pre- to mature miRNA ratio so established is indicative of the state of the cell. We also describe a method comprising the steps of: (a) providing a mesenchymal stem cell (MSC); and (b) introducing an oncogene into the mesenchymal stem cell to thereby transform it; in which the transformed mesenchymal stem cell does not secrete a gene product of the oncogene into a medium in which it is grown.

Abstract: Provided are a method of improving iPS cell establishment efficiency, comprising the step of transferring Lin28B or a nucleic acid that encodes Lin28B to a somatic cell, particularly to a somatic cell on which Lin28 is ineffective or less effective than Lin28B in improving iPS cell establishment efficiency, and a method of producing an iPS cell, comprising the step of transferring Lin28B or a nucleic acid that encodes Lin28B and a nuclear reprogramming substance to a somatic cell. Also provided are an iPS cell comprising a nucleic acid that encodes Lin28B, that can be obtained by the method of producing an iPS cell, and a method of somatic cell production by forcing the iPS cell to differentiate into a somatic cell.

Abstract: The present invention has successfully established a mixed culture system capable of actively proliferating a Kupffer cell in a primary culture of a cell population derived from a liver. Additionally, the present invention has successfully established a novel production method for efficiently producing a large amount of highly purified Kupffer cells using this mixed culture system.

Abstract: In some embodiments, the invention relates to a stable, long-term human ES cell line. In other aspects, the invention relates to methods for establishing a stable long-term ES cell line and methods for screening therapeutic treatments for inner ear diseases, such as Meniere's disease.

Abstract: The present invention provides a method for enhancing the proliferation and/or hematopoietic differentiation and/or maintenance of mammalian stem cells. The method is useful for generating expanded populations of hematopoietic stem cells (HSCs) and thus mature blood cell lineages. This is desirable where a mammal has suffered a decrease in hematopoietic or mature blood cells as a consequence of disease, radiation or chemotherapy. The method of the present invention comprises increasing the intracellular level of a cdx in stem cells, including hematopoietic stem cells, in culture, either by providing an exogenous cdx protein to the cell, or by introduction into the cell of a genetic construct encoding a cdx. The cdx is selected from the cdx family and includes cdx1, cdx2, or cdx4. The cdx may be a wild type protein appropriate for the species from which the cells are derived, or a mutant form of the protein.

Abstract: This invention describes the use of an inductor or activator compound GSE24.2 for producing a medicament or pharmaceutical composition for treating a preferably human illness or pathological situation caused by a senescence process. Said pharmaceutical composition can be useful for a treatment of tissue regeneration, for example of epithelial tissues or haematopoietic cells, and also for the immortalisation of eukaryote cells for use of same in biotechnological research or processes.

Abstract: A method for modulating cell differentiation capabilities using heterologous gene expression. Some embodiments of the invention relate to a method for inducing a cardiac progenitor cell by delivering a reprogramming factor to the cell, wherein the reprogramming factor comprises ETS2 or a combination of ETS2 and Mesp1.

Abstract: The present invention relates to a method for the generation of immortalized transduced cell lines susceptible to senescence whereby the senescence is exogenously inducible and said cells can switch severalfold between the senescent stage and the immortalized stage. In particular, the present invention relates to a method for the generation of immortalized transduced cell lines susceptible to senescence wherein two or more different immortalizing gene sequences have been incorporated whereby said immortalizing gene sequences are regulated by regulators controlled via exogenous means. In a further aspect, the present invention relates to immortalized transduced cell lines obtainable with said method. In addition, methods for screening molecules influencing senescence of cells are provided as well as kits for conducting the same.

Abstract: The present invention generally relates to the fields of genetic engineering and antibody production. In particular, it relates to the generation of genetically modified vertebrate precursor lymphocytes that have the potential to differentiate into more mature lymphoid lineage cells, and to the use thereof for the production of any heterologous antibody or binding protein.

Abstract: The present invention generally relates to the fields of genetic engineering and antibody production. In particular, it relates to the generation of genetically modified vertebrate precursor lymphocytes that have the potential to differentiate into more mature lymphoid lineage cells, and to the use thereof for the production of any heterologous antibody or binding protein.

Abstract: The instant invention provides methods for immortalizing cells. The invention further provides immortalized cell lines, e.g., neuronal cell lines, and methods of using these cell lines in screening assays.

Abstract: The invention provides methods for maintaining cell lines from primary cells, i.e., non-transformed cells, using expression of the signal transducer of activation and transcription (STAT). The methods are particularly suitable for maintenance of B-cells.

Abstract: An apparatus of the invention is for injecting a solution into a cell. The apparatus includes a nozzle that jets a solution to a cell, and a laser irradiating unit that irradiates a laser to the cell to form an opening through which the solution jet from the nozzle is introduced into the cell. The nozzle jets the solution toward a nucleus of the cell, and the laser forms the opening in the cell at a point in a cell membrane of the cell such that the solution can be applied on the nucleus.

Abstract: This invention relates to new immortalized human pre-adipose cell lines capable of differentiating into adipose cells and methods of obtaing the immortalized cells. In particular, the present invention pertains to immortalized pre-adipocyte cell lines derived from white adipose tissue and methods of producing the cell lines. The immortalized pre-adipocyte cells are capable of maturing into immortalized white adipose cells useful in developing drugs, food ingredients and supplements against obesity, diabetes and cardiovascular diseases.