58 results about "Cholangiocyte" patented technology

The invention features methods for increasing or maintaining the number of functional cells of a predetermined type, for example, insulin producing cells of the pancreas, blood cells, spleen cells, brain cells, heart cells, vascular tissue cells, cells of the bile duct, or skin cells, in a mammal (e.g., a human patient) that has injured or damaged cells of the predetermined type.

The invention relates to the field of bioengineering technology, and in particular to a method for in-vitro induction of cholangiocyte-like transformation of primary hepatocytes and for long-term culture, amplification and differentiation and an application of the method. The invention provides a hepatocyte cholangiocyte-like transformation medium determined by chemical ingredients and / or a system which is composed of a hepatocyte mature medium and is applicable to long-term stable culture, amplification and differentiation of the primary hepatocytes; the invention also provides the method for in-vitro induction of cholangiocyte-like transformation of the primary hepatocytes and for long-term culture, amplification and differentiation; and with the application of the method, the cholangiocyte-like hepatocyte conversion of the primary hepatocytes can be induced in vitro, so that the obtained hepatocytes have characteristics of biliary epithelial cells and hepatic precursor cells, and the hepatocytes are applicable to long-term stable culture and amplification. The breedable cholangiocyte-like hepatocytes and hepatocytes, which are mature in differentiation, prepared by the invention are applicable to such aspects as toxicologic and pharmacological evaluation of compounds and drugs, researches and diagnosis & treatment of hepatitis viruses, treatment by hepatocyte transplantation, preparation of bioartificial liver and the like.

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, β-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.The method of producing mammalian progenitors is useful in that the progenitors can be used subsequently in one or more of the following processes: identification of growth and differentiation factors, toxicological studies, drug development, antimicrobial studies, or the preparation of an extracorporeal organ such as a bioartificial liver.

The present invention provides clonal pluripotent hepatic stem cells using flow cytometry and in vitro single-cell-based assays. These cells possess multilineage differentiation potential and self-renewing capability. These cells may be clonally propagated in culture, to continuously produce hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When expanded cells are transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes, with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. Thus, the self-renewing multipotent stem cells persist in the developing mouse liver and can be induced to become cells of other organs of endodermal origin under appropriate microenvironment, providing new insight into therapies for diseases of the digestive system.

Liver progenitor cells immunoreactive for CD117, as well as for CD34 capable of proliferating in a culture; and differentiating in vivo into a hepatocyte, a cholangiocyte or a sinusoidal cell are provided. The cultures can be expanded over a large number of passages and integrate well after transplantation into adult liver.

Hepatic progenitors comprise two populations of human hepatic stem cells, primitive and proximal hepatic stem cells, and two populations of committed progenitors, one for biliary cells and one for hepatocytes. Human primitive hepatic stem cells are a very small fraction of the liver cell population and give rise to proximal hepatic stem cells constituting a much larger fraction of the liver. Human proximal hepatic stem cells give rise to biliary and hepatocyte committed progenitors. Primitive and proximal stem cells are the primary stem cells for the human liver. Human primitive hepatic stem cells may be isolated by immunoselection from human livers or culturing human liver cells under conditions which select for a human primitive hepatic stem cell. Proximal hepatic stem cells may be isolated by immunoselection, or by culturing human liver cells under conditions which include a developmental factor. Proximal hepatic stem cells may also be isolated by culturing colonies comprising a primitive hepatic stem cell under conditions which include a developmental factor. Resulting compositions may be used for treating liver disorders and for producing bioartificial organs.

As discussed in greater detail herein, isolated epitope peptides derived from MPHOSPH1 bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL) and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines. The inventive peptides encompass both the above-mentioned MPHOSPH1-derived amino acid sequences and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted or added, provided such modified versions retain the requisite CTL inducibility of the original sequences. Further provided are polynucleotides encoding any of the aforementioned peptides as well as pharmaceutical agents or compositions that include any of the aforementioned peptides or polynucleotides. The peptides, polynucleotides, and pharmaceutical agents or compositions of this invention find particular utility in either or both of the treatment and prevention of cancers and tumors, including, for example, bladder cancer, breast cancer, cervical cancer, cholangiocellular carcinoma, CML, colorectal cancer, gastric cancer, NSCLC, lymphoma, osteosarcoma, prostate cancer, renal cancer and soft tissue tumor.

The present invention relates to a multipotent stem cell, multipotent cell populations, and an enriched multipotent cell population, each found in fetal, neonatal, pediatric, and adult biliary tree tissue and up to 72 hours post mortem (although preferentially, within 10 hours post mortem) and capable of maturing into multiple endodermal tissues that include liver, biliary and pancreatic tissues. The multipotent stem / progenitor cell and cell populations are found in peribiliary glands, and progenitors descending from them are present throughout the biliary tree including in the gallbladder. High numbers of the peribiliary glands are found in the branching locations of the biliary tree such as hilum, common hepatic duct, cystic duct, common duct, common hepato-pancreatic duct and gallbladder. Related multipotent cells, multipotent cell populations and their descendent progenitors are found throughout the biliary tree including in the gall bladder, which does not have peribiliary glands. Compositions comprising same, methods of identifying and isolating same, maintaining same in culture, expanding same in culture and differentiating or lineage restricting the same in vitro or in vivo to hepatic, biliary or pancreatic fates (e.g., as hepatocytes, cholangiocytes, and / or pancreatic islet cells) are also provided. Methods of using the multipotent cells and / or multipotent cell populations are also provided.

The invention discloses a method for inducing hepatic oval cells to differentiate towards bile duct cells and a special culture medium used in the method. The culture medium is added with 1 to 6 percent of fetal calf serum, 1 to 3 percent of B27 and 0.05 to 0.15 percent of penicillin-streptomycin on the basis of an RPMI1640 culture medium. The method for inducing the differentiation comprises the following steps: 1) leading RhoA mutant genes into the oval cells WB-F344 to obtain WB-F344 cells of a high-expression RhoA gene activity mutant; and 2) inoculating the WB-F344 cells of the high-expression RhoA gene activity mutant into the special culture medium where the hepatic oval cells are induced in vitro to differentiate into the bile duct cells, and culturing the WB-F344 cells at a temperature of 37 DEG C with 5 percent of CO2 to obtain the bile duct cells. The method provides a new approach to obtain the bile duct cells and has wide application prospect.

This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

Isolated peptides derived from SEQ ID NO: 21 and fragments thereof that bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL) and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines, are described herein. The inventive peptides encompass both the above mentioned amino acid sequences and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted or added, provided such modified versions retain the requisite HLA binding and / or CTL inducibility of the original sequences. Further provided are nucleic acids encoding any of the aforementioned peptides as well as pharmaceutical agents, substances and / or compositions that include or incorporate any of the aforementioned peptides or nucleic acids. The peptides, nucleic acids, pharmaceutical agents, substances and compositions of this invention find particular utility in the treatment of cancers and tumors, including, for example, AML, bladder cancer, breast cancer, cervical cancer, cholangiocellular carcinoma, CML, colorectal cancer, esophagus cancer, gastric cancer, gastric diffuse-type cancer, lung cancer, lymphoma, prostate cancer, SCLC and soft tissue tumor.

The present invention relates to a method for diagnosis of bile duct cancer, using methionyl-tRNA synthetase (MRS) in bile duct cells and, more particularly, to a composition for diagnosing bile ductcancer, comprising an agent with which an expression level of methionyl-tRNA synthetase protein is measured, a diagnostic kit, and a method for qualitative or quantitative analysis of MRS to provide information necessary for the diagnosis of bile duct cancer. According to the present invention, MRS retains a very high value as a diagnostic marker for bile duct cancer in terms of rapidity and accuracy because MRS allows determination to be made to see whether bile duct cancer is present or absent for bile duct cells, which have been classified as atypical cells by conventional pathological examination methods. Hence, the present invention provides a method for discriminating between cancer cells and normal cells in atypical cells and can make a definite diagnosis of cancer with almost 100 %in all of sensitivity, specificity, and accuracy in contrast to many conventional cancer markers with which an actual result of diagnosis is substantially difficult to obtain at a cell level (that is, cytodiagnosis).

This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

The invention discloses application of a THBS1 cytokine in preparation of a medicament for treating hepatic failure. The temperature for transport and storage of the THBS1 cytokine-containing medicament is 2-8 DEG C, the humidity is 45-75%, and the THBS1 is a member of an ABCA superfamily and is mainly used for mediating transmembrane transport of lipids. In the application of the THBS1 cytokine in preparation of the medicament for treating hepatic failure, the biochemical indexes of patients can be significantly improved, the bilirubin level is lowered, the transaminase is reduced, the bloodcoagulation function is improved, the albumin level is raised, hepatocyte death is inhibited, regeneration of hepatocytes and bile duct cells is promoted, fatal complications such as major upper gastrointestinal duct bleeding, severe hepatic encephalopathy and hepatorenal syndromes are prevented, the survival time is significantly prolonged, and the survival rate is increased.