Abstract: The present invention relates to a pharmaceutical composition for preventing or treating Fabry disease, containing a TSP1 protein inhibitor as an active ingredient. Particularly, in vascular endothelial cells produced by knocking out a TSP1 gene in induced pluripotent stem cells derived from a Fabry disease patient, of the present invention, the recovery of cell morphology, a decrease in the expression of a TSP1 gene, a decrease in the expression levels of a TSP1 protein and a phosphorylated-SMAD protein, which are anti-angiogenic factors, and an increase in the expression levels of a KDR protein and an eNOS protein, which are angiogenic factors, have been confirmed, and thus a TSP1 gene expression inhibitor or a TSP1 protein activity inhibitor can be effectively used in the treatment of Fabry disease.

Abstract: The present invention relates to a pharmaceutical composition for the prevention or treatment of CFC (cardiofaciocutaneous) syndrome comprising a TGF-? signaling pathway inhibitor or a BMP signaling pathway activator. The treatment of SB-431542 or BMP4 protein was confirmed to increase the ALP activity and bone mineral deposition in the osteoblasts originated from the induced pluripotent stem cells derived from CFC syndrome patients. Thus, the TGF-? signaling pathway inhibitor containing SB-431542 or the BMP signaling pathway activator containing BMP4 protein can be effectively used for the prevention or treatment of CFC syndrome.

Abstract: The present invention relates to a pharmaceutical composition for the prevention or treatment of CFC (cardiofaciocutaneous) syndrome comprising a TGF-? signaling pathway inhibitor or a BMP signaling pathway activator. The treatment of SB-431542 or BMP4 protein was confirmed to increase the ALP activity and bone mineral deposition in the osteoblasts originated from the induced pluripotent stem cells derived from CFC syndrome patients. Thus, the TGF-? signaling pathway inhibitor containing SB-431542 or the BMP signaling pathway activator containing BMP4 protein can be effectively used for the prevention or treatment of CFC syndrome.

Abstract: The present invention relates to a pharmaceutical composition for the prevention or treatment of CFC (cardiofaciocutaneous) syndrome comprising a TGF-? signaling pathway inhibitor or a BMP signaling pathway activator. The treatment of SB-431542 or BMP4 protein was confirmed to increase the ALP activity and bone mineral deposition in the osteoblasts originated from the induced pluripotent stem cells derived from CFC syndrome patients. Thus, the TGF-? signaling pathway inhibitor containing SB-431542 or the BMP signaling pathway activator containing BMP4 protein can be effectively used for the prevention or treatment of CFC syndrome.

Abstract: The present invention relates to an induced pluripotent stem cell model of Fabry disease, a preparation method thereof, and a use of the same for the study of Fabry disease development and for the screening of a therapeutic agent for the disease. Particularly, Fabry disease derived induced pluripotent stem cells (iPSCs), embryoid body (EB), and vascular cells were developed and differentiated from fibroblasts originated from Fabry disease patient, wherein the Fabry disease originated iPSCs displayed significantly reduced expression and activity of GLA protein therein, compared with the normal cells, resulting in the accumulation of globotriaosylceramide (Gb3, CD77). Also, the differentiation of vascular cells was induced from the Fabry disease originated iPSCs, and as a result the iPSCs were successfully differentiated into vascular endothelial cells and vascular smooth muscle cells with significantly expressing the marker protein.

Abstract: The present invention relates to an induced pluripotent stem cell (iPS) model for cardiofaciocutaneous (CFC) syndrome, a method for producing the model, and uses of the iPS model in the analysis of neural development in CFC syndrome. Specifically, the CFC syndrome-derived iPS and generation and differentiation of an embryonic body were induced from the fibroblasts of a CFC syndrome patient, and the CFC syndrome-derived iPS and embryonic body were confirmed to exhibit broken embryonic body shapes and no differentiation into neurons. When a CFC syndrome-derived embryonic body was induced by treating with p-ERK and p-SMAD1 inhibitors, the embryonic body exhibited a normal embryonic body shape and effectively differentiated into neurons. Thus, the CFC syndrome patient-derived stem cell model of the invention can be effectively used in the research for neural development in cardiofaciocutaneous syndrome.

Abstract: The present invention relates to a method for improving drug metabolism function of human stem cell-derived hepatocytes. More precisely, the human stem cell-derived hepatocytes are similar in cell morphology to human hepatocytes but display reduced expressions of drug or alcohol metabolism associated enzymes and antioxidant enzymes. So, the inventors co-cultured the hepatocytes differentiated from human stem cells with mouse hepatic stellate cells. As a result, it was confirmed that alcohol mediated toxicity was reduced so that liver cell damage or apoptosis level was reduced. In the meantime, the expressions of drug and alcohol metabolism associated enzymes and antioxidant enzymes were increased.

Abstract: The present invention prepared insulin-producing endocrine cells by inducing the differentiation of human embryonic stem cells or human induced pluripotent stem cells into definitive endoderm (DE), pancreatic endoderm (PE), endocrine progenitors (EP), and endocrine cells (EC) stepwise in that order. Particularly, the present invention established the conditions for the formation of an insulin producing endocrine aggregate (EA) from the endocrine cells. Especially in this invention, it was confirmed that the endocrine aggregate has the cell proliferation potential at a significant level and has the increased insulin productivity as well as the activity of inhibiting cell necrosis and apoptosis. Therefore, the method for preparing the endocrine aggregate of insulin-producing beta cells from human pluripotent stem cells can be effectively used for the examination of the medicinal effect of the conventional antidiabetic agents and of the novel antidiabetic drugs.

Abstract: The present invention relates to a composition for the prevention and treatment of liver toxicity originated from acetaminophen comprising TNP (N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine) as an active ingredient. The present inventors confirmed that TNP known as a 5-inosito pyrophosphate inhibitor suppressed apoptosis caused by acetaminophen in human embryonic stem cell-derived liver cells, mouse liver cells, and human hepatoma cell lines, up-regulated glutathione converted in liver cells, and inhibited JNK phosphorylation that is a kind of response against stress increased by acetaminophen. The inventors further confirmed that TNP had the activity of protecting liver cells from the toxicity caused by acetaminophen in an animal model. Therefore, TNP can be efficiently used as an active ingredient for a composition for the prevention and treatment of liver toxicity caused by acetaminophen.

Abstract: The present invention relates to an immune hepatotoxicity screening method using hepatocytes derived from human stem cells. After hepatocytes differentiated from human stem cells and human hepatocytes are treated with ethanol, CCl4, and acetaminophen to induce immune hepatotoxicity, a hepatocellular immunotoxic material assay system is constructed in order to verify cytokines, chemokines, and lipid mediators, which are mediators secreted from the hepatocytes, and an immunotoxic material can be confirmed in the cells having the induced hepatotoxicity by using the system. Therefore, the immune hepatotoxicity screening method using hepatocytes derived from human stem cells can be favorably used.

Abstract: The present invention relates to an induced pluripotent stem cell (iPSC) model of Noonan syndrome, a preparation method thereof, and uses to study of the pathogenesis of Noonan syndrome and a therapeutic agent screening method. Particularly, induced pluripotent stem cells from dermal fibroblasts of a Noonan syndrome-patient (NS-iPSCs) were generated, and differentiated into embryoid bodies (EBs), neural rosettes and neural cells. These iPSCs exhibited the normal morphology while showed reduced differentiation potency compare to control cell lines. NS-iPSCs were developed into embryoid bodies and neural rosettes by naturally and chemically directed differentiation. Interestingly, embryoid bodies and neural rosettes induced via chemically directed differentiation exhibited normal morphology and expressed ectoderm, neural rosettes and neural marker genes similar to normal cells.

Abstract: The present invention relates to a composition for the prevention and treatment of liver toxicity originated from acetaminophen comprising TNP (N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine) as an active ingredient. The present inventors confirmed that TNP known as a 5-inosito pyrophosphate inhibitor suppressed apoptosis caused by acetaminophen in human embryonic stem cell-derived liver cells, mouse liver cells, and human hepatoma cell lines, up-regulated glutathione converted in liver cells, and inhibited JNK phosphorylation that is a kind of response against stress increased by acetaminophen. The inventors further confirmed that TNP had the activity of protecting liver cells from the toxicity caused by acetaminophen in an animal model. Therefore, TNP can be efficiently used as an active ingredient for a composition for the prevention and treatment of liver toxicity caused by acetaminophen.

Abstract: The present invention relates to an induced pluripotent stem cell (iPS) model for cardiofaciocutaneous (CFC) syndrome, a method for producing the model, and uses of the iPS model in the analysis of neural development in CFC syndrome. Specifically, the CFC syndrome-derived iPS and generation and differentiation of an embryonic body were induced from the fibroblasts of a CFC syndrome patient, and the CFC syndrome-derived iPS and embryonic body were confirmed to exhibit broken embryonic body shapes and no differentiation into neurons. When a CFC syndrome-derived embryonic body was induced by treating with p-ERK and p-SMAD1 inhibitors, the embryonic body exhibited a normal embryonic body shape and effectively differentiated into neurons. Thus, the CFC syndrome patient-derived stem cell model of the invention can be effectively used in the research for neural development in cardiofaciocutaneous syndrome.

Abstract: The present application describes a method of creating cardioblasts and cardiomyocytes.

Abstract: The present invention relates to an induced pluripotent stem cell model of Fabry disease, a preparation method thereof, and a use of the same for the study of Fabry disease development and for the screening of a therapeutic agent for the disease. Particularly, Fabry disease derived induced pluripotent stem cells (iPSCs), embryoid body (EB), and vascular cells were developed and differentiated from fibroblasts originated from Fabry disease patient, wherein the Fabry disease originated iPSCs displayed significantly reduced expression and activity of GLA protein therein, compared with the normal cells, resulting in the accumulation of globotriaosylceramide (Gb3, CD77). Also, the differentiation of vascular cells was induced from the Fabry disease originated iPSCs, and as a result the iPSCs were successfully differentiated into vascular endothelial cells and vascular smooth muscle cells with significantly expressing the marker protein.

Abstract: The present invention prepared insulin-producing endocrine cells by inducing the differentiation of human embryonic stem cells or human induced pluripotent stem cells into definitive endoderm (DE), pancreatic endoderm (PE), endocrine progenitors (EP), and endocrine cells (EC) stepwise in that order. Particularly, the present invention established the conditions for the formation of an insulin producing endocrine aggregate (EA) from the endocrine cells. Especially in this invention, it was confirmed that the endocrine aggregate has the cell proliferation potential at a significant level and has the increased insulin productivity as well as the activity of inhibiting cell necrosis and apoptosis. Therefore, the method for preparing the endocrine aggregate of insulin-producing beta cells from human pluripotent stem cells can be effectively used for the examination of the medicinal effect of the conventional antidiabetic agents and of the novel antidiabetic drugs.

Abstract: The present invention relates to a composition for inducing embryonic stem cell differentiation comprising a MEK/ERK (mitogen-activated protein kinase kinase/extracellular regulated kinase) signal transduction inhibitor and BMP (bone morphogenetic protein), and a method for inducing differentiation of embryonic stem cells into mesodermal cells using the same. Further, the mesodermal cells obtained by the above method are able to differentiate into various mesenchymal tissue cells. In particular, the present invention relates to a method for inducing differentiation into hemangioblast by culturing the mesodermal cells obtained by the above method in the presence of VEGF (vascular endothelial cell growth factor) and bFGF (basic fibroblast growth factor). The differentiated hemangioblasts can be further differentiated into vascular endothelial cells, vascular smooth muscle cells, and hematopoietic stem cells under various culture conditions.

Abstract: The present invention relates to a bovine beta-casein gene targeting vector comprising (1) a first region having a length of 5 to 12 kb which is homologous to the promoter and its flanking nucleic acid sequences of bovine beta-casein gene, and comprising exon 1, intron 1, and exon 2 of bovine beta-casein gene; (2) a region for cloning a nucleic acid coding for desired proteins; (3) a region for coding a positive selection marker; (4) a second region having a length of 2.8 to 3.5 kb which is homologous to the nucleic acid sequences of bovine beta-casein gene, and comprising exon 5, 6, 7 and 8, and intron 5, 6 and 7 of bovine beta-casein gene; wherein the nucleic acid segment corresponding to the first region is located upstream to the nucleic acid segment corresponding to the second region in the 5?-3? arrangement of beta-casein gene.

Abstract: The present invention relates to a composition for inducing embryonic stem cell differentiation comprising a MEK/ERK (mitogen-activated protein kinase kinase/extracellular regulated kinase) signal transduction inhibitor and BMP (bone morphogenetic protein), and a method for inducing differentiation of embryonic stem cells into mesodermal cells using the same. Further, the mesodermal cells obtained by the above method are able to differentiate into various mesenchymal tissue cells. In particular, the present invention relates to a method for inducing differentiation into hemangioblast by culturing the mesodermal cells obtained by the above method in the presence of VEGF (vascular endothelial cell growth factor) and bFGF (basic fibroblast growth factor). The differentiated hemangioblasts can be further differentiated into vascular endothelial cells, vascular smooth muscle cells, and hematopoietic stem cells under various culture conditions.

Abstract: The present invention relates to a bovine beta-casein gene targeting vector comprising (1) a first region having a length of 5 to 12 kb which is homologous to the promoter and its flanking nucleic acid sequences of bovine beta-casein gene, and comprising exon 1, intron 1, and exon 2 of bovine beta-casein gene; (2) a region for cloning a nucleic acid coding for desired proteins; (3) a region for coding a positive selection marker; (4) a second region having a length of 2.8 to 3.5 kb which is homologous to the nucleic acid sequences of bovine beta-casein gene, and comprising exon 5, 6, 7 and 8, and intron 5, 6 and 7 of bovine beta-casein gene; wherein the nucleic acid segment corresponding to the first region is located upstream to the nucleic acid segment corresponding to the second region in the 5?-3? arrangement of beta-casein gene.