Abstract: A rotating wall vessel is used as a culture vessel and bioreactor for the cultivation of hepatocytes in the form of spheroids to generate a culture with many properties of the intact liver. These properties include enzyme activity comparable to fresh cells and long-term maintenance of viability and cellular function for periods on the order of months. The cultures may be used to produce hepatocyte products, evaluate metabolism of an agent, propagate Hepatitis C virus and test agents as inhibitors of this virus. Thus, the culture system disclosed herein makes long term functional cultivation of human hepatocytes feasible.

Abstract: A rotating wall vessel is used as a culture vessel and bioreactor for the cultivation of hepatocytes in the form of spheroids to generate a culture with many properties of the intact liver. These properties include enzyme activity comparable to fresh cells and long-term maintenance of viability and cellular function for periods on the order of months. The cultures may be used to produce hepatocyte products, evaluate-metabolism of an agent, propagate Hepatitis C virus and test agents as inhibitors of this virus. Thus, the culture system disclosed herein makes long term functional cultivation of human hepatocytes feasible.

Abstract: This invention relates to virally-immortalized hepatocyte cell lines, which are derived from a normal primary human liver cell, have the ability to proliferate in a serum-free media, are nontumorigenic, and produce proteins. These cell lines can be used for toxicity testing of potential therapeutic drugs and chemical entities. The cell lines may also be used for the production of therapeutic plasma proteins.

Abstract: The present invention relates to the qualitative and quantitative validation of marker indices, especially for medical diagnosis and particularly for the determination of the growth fraction in a sample with antibodies against the Ki-67 protein. Diagnostic kit for the quantification of a cell fraction labeled by a marker for in vitro diagnosis, characterized in that a pseudo-tissue is used for the intra- and inter-assay standardization of the marker index.

Abstract: Transplanting human hepatocytes into a liver of an immunodeficient hepatopathy mouse, and then feeding the mouse transplanted with the human hepatocytes under such a condition as being protected from the attack by human complement produced by the human hepatocytes thereby proliferating the transplanted human hepatocytes in the mouse liver. Further, obtaining human hepatocytes in large scale by repeating the above steps using the proliferated human hepatocytes.

Abstract: The present invention relates to the discovery of immortalized neonatal human hepatocytes that exhibit phenotypic features of human hepatic progenitor cells. The invention is also directed to a method of obtaining telomerase-immortalized neonatal human hepatocytes that exhibit phenotypic features of human hepatic progenitor cells. Furthermore, the instant invention describes methods of using the immortalized neonatal human hepatocytes in cellular therapies, toxicological studies, pharmacokinetic studies, metabolic studies, therapeutic gene delivery and for the production of fully differentiated hepatocytes.

Abstract: The present invention provides a reversibly immortalized mammalian liver cell line, especially CYNK-1 (deposited with International Patent Organism Depository, National Institute of Advanced Industrial Science and Technology, address: AIST Tsukuba Central 6, 1-1, Higashi 1-Chome, Tsukuba-shi, Ibaraki-ken, 305-8566 Japan, deposited date: Mar. 10, 2004, accession number: FERM BP-08657) comprising an immortalizing gene interposed between a pair of site-specific recombination sequences and a suicide gene in the outside of the pair of site-specific recombination sequences, characterized in that the suicide gene can exhibit its function after excision of the pair of site-specific recombination sequences, or passage cell line thereof; a mammalian liver cell obtained by excising the immortalizing gene from the reversibly immortalized mammalian liver cell line or passage cell line thereof; and use of these cells.

Abstract: Vectors capable of stably integrating a transgene in the genome of a non-dividing cell or of a slowly-dividing cell, said vector comprising or expressing at least one immortalization molecule and cells immortalized with said vectors.

Abstract: Methods of inducing differentiation of stem cells and stem cells obtained are disclosed. A method for stabilizing the phenotype of isolated primary cells in vitro is disclosed. In both methods, a central role is played by histone deacetylase inhibitors.

Abstract: The present invention relates to a novel hepatocyte-like cell progenitor and/or a novel hepatocyte-like cell derived via definitive endoderm from human blastocyst-derived stem (hBS) cells, to a method for the preparation of such cells and to the potential use of such cells in e.g. pharmaceutical drug discovery and development, toxicity testing, cell therapy and medical treatment. In particular is presented a definitive endoderm derived hepatocyte-like cell with important liver-expressed marker genes and important metabolizing enzymes, as well as drug transporters.

Abstract: A method of inducing liver regeneration in a damaged liver tissue region of an individual is provided. The method including the step of providing at least two distinct growth factors to the damaged liver tissue region of the individual, at least one of the at least two distinct growth factors being an angiogenic factor.

Abstract: The present invention relates to an assay system and method for testing compounds for their ability to regulate the hepatic lipase (HL) promoter. In particular, the invention relates to the identification of estrogen receptor ligands having this activity. Compounds that inhibit HL promoter activity are useful as leads, or on their own, to develop therapeutics in the prevention of heart disease.

Abstract: The present invention provides a mammalian immortalized liver cell obtained by transferring a cell proliferation factor gene located between a pair of site-specific recombination sequences into a mammalian liver cell.

Abstract: The present invention is directed to monoclonal, chimeric or humanized, antibodies or antibody-like molecules that recognize an epitope common to human acidic and basic isoferritins. The anti-ferritin antibodies or antibody-like molecules can be used in pharmaceutical compositions for immunotherapy or radioimmunotherapy to target various cancer cells in a mammal. A method for delivering anti-ferritin antibodies or antibody-like molecules to cancerous lymph cells, pancreatic cells, lymphatic endothelium cells, and liver cells is also disclosed, as well as methods for treating pancreatic cancer, hepatocellular carcinomas, Kaposi's sarcoma and Hodgkin's lymphoma.

Abstract: The present invention is directed to compounds of formula (I): where X, Y, R1, R2 and R3 are defined therein, which can act as modulators of viral replication and/or virus production, especially of the hepatitis C virus (HCV).

Abstract: This invention relates to an isolated nucleotide fragment of a novel estrogen receptor, in particular, a novel ER? variant protein and isolated nucleic acid fragment comprising the coding regions of the genes encoding such variant proteins. Also provided are vectors, host cells, and methods for producing the novel ER? variant protein. The invention further relates to method of obtaining such nucleotide fragment and the method of determining the presence of such ER? variant protein in a sample.

Abstract: A method of propagating mammalian endodermally derived progenitors such as hepatic progenitors, their progeny, or mixtures thereof is developed which includes culturing mammalian progenitors, their progeny, or mixtures thereof on a layer of embryonic mammalian feeder cells in a culture medium. The culture medium can be supplemented with one or more hormones and other growth agents. These hormones and other growth agents can include insulin, dexamethasone, transferrin, nicotinamide, serum albumin, ?-mercaptoethanol, free fatty acid, glutamine, CuSO4, and H2SeO3. The culture medium can also include antibiotics. Importantly, the culture medium does not include serum. The invention includes means of inducing the differentiation of the progenitors to their adult fates such as the differentiation of hepatic progenitor cells to hepatocytes or biliary cells by adding, or excluding epidermal growth factor, respectively.

Abstract: The present invention relates to a gene derived from a novel fulminant hepatitis C virus strain, an HCV replicon RNA with a high replication efficiency obtained using the gene, and an HCV replicon-replicating cell transfected with the replicon RNA. When the HCV replicon RNA and the HCV replicon-replicating cell of the present invention are used, HCV proteins can be continuously produced in a large amount.

Abstract: A serum-free C3A clonal cell line and methods for generating the same are provided. The C3A cell line has a reduced doubling time in serum-free medium compared to a corresponding C3A cell line from which it is derived. Methods using the cells of the serum-free C3A clonal cell line for the production, expression and recovery of harvestable polypeptides, screening compounds for metabolic activity, studying enteric disease and for use in a bio-artificial liver device are also provided.

Abstract: This disclosure provides a newly developed strategy and particular options for differentiating pluripotent stem cells into cells of the hepatocyte lineage. Many of the protocols are based on a strategy in which the cells are first differentiated into early germ layer cells, then into hepatocyte precursors, and then into mature cells. The cells obtained have morphological features and phenotypic markers characteristic of human adult hepatocytes. They also show evidence of cytochrome p450 enzyme activity, validating their utility for commercial applications such as drug screening, or use in the manufacture of medicaments and medical devices for clinical therapy.

Abstract: The invention is the modification of organs, tissues and cells with a storage/reperfusion solution comprising siRNAs specific for genes whose expression is associated with loss of viability or cell damage. The presence of siRNAs in the storage/reperfusion solution minimizes and/or prevents organ, tissue and cell damage such that the organs, tissues or cells can be used for in vivo transplantation. The invention is also directed generally to methods for maintaining organs, tissues and cells in a viable state using the storage/reperfusion solution.

Abstract: Isolated liver progenitor stem cells and cell populations of isolated liver progenitor stem cells are disclosed. The progenitor stem cells originate from adult liver, especially human adult liver. The isolated progenitor stem cells have uses in medicine, hepatology, inborn errors of liver metabolism transplantation, infectious diseases and liver failure. Methods of isolating these cells and their culture is described. The isolated cells are characterized before and after differentiation. Their use for transplantation and as animal models of human disease, toxicology and pharmacology is disclosed.

Abstract: The present invention relates to at least one novel chimeric, humanized or CDR-grafted anti-IL-6 antibodies derived from the murine CLB-8 antibody, including isolated nucleic acids that encode at least one such anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The present invention relates to immortal pluripotent stem cells derived from a human leukaemia cell line, preferably a human monocytoid cell line and more preferably the human monocytoid cell line, THP1. The present invention further relates to cell lines derived from the immortal pluripotent stem cell line having the phenotype of cell strains characteristic of human tissues, particularly having a human hepatocyte phenotype, as well as the methods for preparing thereof. The present invention further relates to the use of the derived cell line with a human hepatocytic phenotype for the production of albumin and blood coagulation factors.

Abstract: This invention relates generally to cells and cell lines that are permissive for hepatitis C virus (HCV) replication, and methods and materials for making and using them. The subject cell line referred to as Huh-7.5 has the A.T.C.C. designation number PTA-8561, having been deposited on Aug. 1, 2007.

Abstract: Human hepatoma cell lines are provided that comprises a set of cells clonally derived from a cancerous human liver cell, in which each cell of the set expresses a receptor having an affinity for binding a virus of the Flaviviridae genus and a virus of the Hepadnaviridae genus to enable infection by viruses of both genus in native forms, and in which each cell of the set exhibits susceptibility to infection by a hepatotropic parasite of the Leishmania genus in a native form. Various compositions and methods relating to diagnostic, therapeutic, and prophylactic embodiments are also provided.

Abstract: A method of propagating mammalian endodermally derived progenitors such as hepatic progenitors, their progeny, or mixtures thereof is developed which includes culturing mammalian progenitors, their progeny, or mixtures thereof on a layer of embryonic mammalian feeder cells in a culture medium. The culture medium can be supplemented with one or more hormones and other growth agents. These hormones and other growth agents can include insulin, dexamethasone, transferrin, nicotinamide, serum albumin, ?-mercaptoethanol, free fatty acid, glutamine, CuSO4, and H2SeO3. The culture medium can also include antibiotics. Importantly, the culture medium does not include serum. The invention includes means of inducing the differentiation of the progenitors to their adult fates such as the differentiation of hepatic progenitor cells to hepatocytes or biliary cells by adding, or excluding epidermal growth factor, respectively.

Abstract: The invention relates to processes for the preparation of liver cells for cryopreservation, processes for cryopreservation of isolated liver cells and processes for the preparation of a culture of cryopreserved isolated liver cells.

Abstract: The present invention provides novel cell-based and animal-based assays for determining antagonists of PKC? and uses of the isolated antagonist compounds for modulating insulin clearance and secretion. The invention also provides novel animals and cells such as animals and cells suitable for use in the assays.

Abstract: A cryopreservation medium comprising a protein-containing plant extract is disclosed. Methods, compositions, uses and kits for cryopreservation of biological material, such as a molecule, organelle, cell, embryo, tissue or organ, are also disclosed.

Abstract: The invention provides for methods of screening for compounds that increase the expression of P-selectin, SDF-1, and/or CXCR4 on facilitatory cells (FCs). The invention also provides for methods of screening for compounds that increase the level of p-predendritic cells (p-pre DC) without substantially decreasing the level of natural killer (NK) cells in a population of FCs. The invention further provides for methods of characterizing the facilitating capability of FCs by evaluating such cells for the amount of P-selectin, SDF-1, and/or CXCR4.

Abstract: HCV variants are described. The variants include polynucleotides comprising non-naturally occurring HCV sequences and HCV variants that have a transfection efficiency and ability to survive subpassage greater than HCV that have wild-type polyprotein coding regions. Expression vectors comprising the above polynucleotides and HCV variants are also described, as are the provision of cells and host cells comprising the expression vectors. Methods for identifying a cell line that is permissive for infection with HCV are also provided, as are vaccines comprising the above polynucleotides in a pharmaceutically acceptable carrier. Additionally, methods for inducing immunoprotection to HCV in a primate are described, as are methods for testing a compound for inhibiting HCV replication.

Abstract: With respect to a method for differentially inducing embryo-stem cells into hepatocytes, in order to obtain safe hepatocytes that are adequately functionable and able to supply in large quantity, a method for differentially inducing embryo-stem cell into hepatocyte, wherein the embryo-stem cells are cultured in the presence of deletion type hepatocyte growth factor is provided. Further, a method for differentially inducing embryo-stem cells into hepatocytes comprising (a) a step of forming the embryoid body of the embryo-stem cells and (b) a step of culturing the embryoid body in the presence of deletion type hepatocyte growth factor is provided.

Abstract: This invention provides a system for rapid determination of pharmacologic effects on target tissue types in cell populations cultured in vitro. The cells contain a promoter-reporter construct that reflects a toxicologic or metabolic change caused by the agent being screened. The promoter is taken from a gene known to be up- or down-regulated according to the metabolic state of the cell, and linked to a reporter gene that provides an external signal for monitoring promoter activity. The promoter-reporter cells may be produced by placing these genetic alterations into a line of human embryonic stem cells, bulking up the cells to any extent desired, and then differentiating the cells into the desired tissue type. This disclosure explains some of the powerful features of the promoter-reporter cells of this invention, and shows various ways the skilled reader can use the invention for pharmaceutical development and testing, or to monitor graft survival.

Abstract: A serum-free C3A clonal cell line and methods for generating the same are provided. The C3A cell line has a reduced doubling time in serum-free medium compared to a corresponding C3A cell line from which it is derived. Methods using the cells of the serum-free C3A clonal cell line for the production, expression and recovery of harvestable polypeptides, screening compounds for metabolic activity, studying enteric disease and for use in a bio-artificial liver device are also provided.

Abstract: The invention relates to the production of hepatocyte cell lines useful in toxicology screens or therapy. A mammalian hepatocyte comprises, as a single polypeptide, a fusion protein comprising a c-myc protein and an oestrogen receptor, or functional fragments thereof.

Abstract: The invention relates to the discovery of a selective cell surface marker that permits the selection of a unique subset of pancreatic stems cells having a high propensity to differentiate into insulin producing cells or into insulin producing cell aggregates.

Abstract: ANGPTL4 compositions and methods of using such compositions, and agonists or antagonists thereof, for the diagnosis and treatment of diseases or disorders are included, including methods to modulate cell proliferation, cell adhesion, and cell migration.

Abstract: The disclosure relates to isolated nucleic acid sequences obtainable from the genome of the HXHV virus, specifically, nucleic acid sequences comprising the sequence identified by SEQ ID NO: 4 or the complementary sequence to SEQ ID NO: 4, and to polypeptides coded by the nucleic acid sequences and uses thereof.

Abstract: The present invention provides a cell line capable producing infectious hepatitis C virus 1a (HCV 1a) particles in culture. Disclosed are compositions and methods for an HCV 1a (clone H77) transfected immortal human hepatocyte (IHH) capable of generating infectious HCV 1a virus particles in culture. Also disclosed are methods of using the cell line, or HCV 1a virus particles derived from said cell line, to screen for potential therapeutic agents which interfere with HCV 1a virus propagation to treat hepatic disease.

Abstract: A rotating wall vessel is used as a culture vessel and bioreactor for the cultivation of hepatocytes in the form of spheroids to generate a culture with many properties of the intact liver. These properties include enzyme activity comparable to fresh cells and long-term maintenance of viability and cellular function for periods on the order of months. The cultures may be used to produce hepatocyte products, evaluate metabolism of an agent, propagate Hepatitis C virus and test agents as inhibitors of this virus. Thus, the culture system disclosed herein makes long term functional cultivation of human hepatocytes feasible.

Abstract: A unique HCV RNA molecule is provided having an enhanced efficiency of establishing cell culture replication. Novel adaptive mutations have been identified within the HCV non-structural region that improves the efficiency of establishing persistently replicating HCV RNA in cell culture. This self-replicating polynucleotide molecule contains, contrary to all previous reports, a 5?-NTR that can be either an A as an alternative to the G already disclosed and therefore provides an alternative to existing systems comprising a self-replicating HCV RNA molecule. The G-->A mutation gives rise to HCV RNA molecules that, in conjunction with mutations in the HCV non-structural region, such as the G(2042)C/R mutations, possess greater efficiency of transduction and/or replication. These RNA molecules when transfected in a cell line are useful for evaluating potential inhibitors of HCV replication.

Abstract: The present invention provides methods for inducing the differentiation of pluripotent cells. The present inventors succeeded in differentiating hepatocytes from ES cells without EB formation, using simple adherent monoculturing in media comprising several growth factors in culture dishes with two different matrices.

Abstract: The present invention is a novel nucleic acid sequence which hybridizes to SEQ ID NO:6 or fragments thereof under stringent conditions, or fragments thereof. The invention also includes diagnostic assays, expression vectors, control sequences, antisense molecules, ribozymes, and host cells to express the polypeptide encoded by the nucleic acid sequence. The present invention also includes claims to the polypeptide sequence coded by the nucleic acid sequences.

Abstract: The present invention relates to a replicon RNA comprising a nucleotide sequence at least containing the 5? untranslated region, the nucleotide sequence encoding NS3 protein, NS4A protein, NS4B protein, NS5A protein and NS5B protein, and the 3? untranslated region on the genomic RNA of hepatitis C virus of genotype 2a.

Abstract: It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function.

Abstract: The present invention relates to a method for improving homogeneity and/or secretion of a recombinant protein of interest expressed in mammalian cells by replacing the endogenous signal peptide sequence of the DNA encoding the protein of interest with that of human hGH. Specifically, the present invention relates to a method wherein the protein of interest is a subunit of the follicle stimulating hormone (FSH). The invention also relates to DNA expression vectors containing the sequence encoding such proteins of interest fused to the signal peptide sequence of the hGH and to cells harbouring such vectors.

Abstract: It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function.

Abstract: The invention relates to gene delivery vehicles which comprise nucleic acid molecules encoding apoptosis-inducing proteins VP2 and/or apoptin (VP3) like activity. VP2 and VP3 are viral proteins of the Chicken Anaemia Virus. Also, the invention relates to anti-tumor therapies. Infection of various human tumor cells with the gene delivery vehicles of the invention will result in the induction of apoptosis in tumor cells and much reduced apoptosis, if at all, in normal diploid, non-transformed/non-malignant cells. Also the invention relates to the diagnosis of cancer, and related forms of hyperplasia, metaplasia and dysplasia.

Abstract: Cell based assays are used to assess the hepatotoxicity of a stimulus. Imaging technologies are used to analyze the effects of a stimulus on hepatocytes. Image analysis may characterize the stimulus on the basis of whether it is hepatotoxic, and if so what type of pathology is exhibited; e.g., apoptosis, necrosis, cholestasis, and/or steatosis.