公开(公告)号：US20170016886A1

公开(公告)日：2017-01-19

申请号：US15221217

申请日：2016-07-27

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Yong-Mahn HAN ,  Young Hee Ju

IPC: G01N33/50

CPC classification number: G01N33/5073 ,  C12N5/0618 ,  C12N5/0696 ,  C12N2506/1307 ,  C12N2506/45 ,  G01N33/5023 ,  G01N33/5026 ,  G01N33/5058 ,  G01N2800/385

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. Thus, the cellular model can be useful in analytical research to understand pathogenesis of Noonan syndrome and establish screening method of the therapeutic agent.

Abstract translation: 本发明涉及Noonan综合征的诱导多能干细胞（iPSC）模型及其制备方法，用于研究Noonan综合征的发病机理和治疗剂筛选方法。 特别是，产生了一个Noonan综合征患者（NS-iPSCs）的真皮成纤维细胞诱导的多能干细胞，并分化为胚状体（EB），神经花环和神经细胞。 与对照细胞系相比，这些iPSC显示出正常的形态，同时显示出降低的分化效力。 NS-iPSCs通过自然和化学指导的分化发育成胚状体和神经花环。 有趣的是，通过化学指导的分化诱导的胚状体和神经花环呈现与正常细胞相似的正常形态和表达的外胚层，神经花环和神经标记基因。 因此，细胞模型可用于分析研究，以了解Noonan综合征的发病机制，并建立治疗药物的筛选方法。

公开(公告)号：US20160355788A1

公开(公告)日：2016-12-08

申请号：US15103271

申请日：2013-12-11

Applicant: Korea Advanced Institute of Science and Technology

Inventor： Yong-Mahn HAN ,  Kyu-Min HAN

IPC: C12N5/074 ,  C12Q1/68 ,  G01N33/50

CPC classification number: C12N5/0696 ,  C12N5/0618 ,  C12N2503/00 ,  C12N2506/45 ,  C12Q1/6881 ,  C12Q1/6883 ,  C12Q2600/158 ,  G01N33/5073

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 translation: 本发明涉及用于心脏皮下（CFC）综合征的诱导多能干细胞（iPS）模型，该模型的制备方法以及iPS模型在CFC综合征神经发育分析中的应用。 具体来说，从CFC综合征患者的成纤维细胞诱导了来自CFC综合征的iPS和胚胎体的产生和分化，并且证实了来自CFC综合征的iPS和胚胎体表现出破碎的胚胎体形状，并且没有分化成神经元 。 当通过用p-ERK和p-SMAD1抑制剂处理诱导CFC综合征衍生的胚胎体时，胚体表现出正常的胚胎体形状并有效地分化为神经元。 因此，本发明的CFC综合征患者来源的干细胞模型可以有效地用于心脏皮肤综合征神经发育的研究。

公开(公告)号：US20180163179A1

公开(公告)日：2018-06-14

申请号：US15123027

申请日：2015-03-17

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Won-il JEONG ,  Yong-Mahn HAN ,  Mi Young KIM ,  Hyuk Soo EUN ,  Mi-Jin JANG

IPC: C12N5/071 ,  C12Q1/32 ,  C12Q1/30 ,  C12Q1/26

CPC classification number: C12N5/0672 ,  C12N5/067 ,  C12N2500/38 ,  C12N2501/12 ,  C12Q1/02 ,  C12Q1/26 ,  C12Q1/30 ,  C12Q1/32 ,  G01N33/50

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.

公开(公告)号：US20170052172A1

公开(公告)日：2017-02-23

申请号：US15257338

申请日：2016-09-06

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Seung-Hyo LEE ,  Seyun KIM ,  Yong-Mahn HAN

IPC: G01N33/50 ,  C12N5/071

CPC classification number: G01N33/5067 ,  C12N5/067 ,  C12N2501/119 ,  C12N2501/12 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2506/02

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 translation: 本发明涉及使用源自人干细胞的肝细胞的免疫肝毒性筛选方法。 肝细胞分化为人干细胞后，用乙醇，CCl4和对乙酰氨基酚处理肝细胞诱导免疫肝毒性，构建了一种肝细胞免疫毒素物质测定系统，以验证细胞因子，趋化因子和脂质介质，这些介质是从 可以通过使用该系统在具有诱导的肝毒性的细胞中确认肝细胞和免疫毒性物质。 因此，可以有利地使用使用源自人干细胞的肝细胞的免疫肝毒性筛选方法。

公开(公告)号：US20160354378A1

公开(公告)日：2016-12-08

申请号：US15032295

申请日：2015-07-03

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Seyun KIM ,  Yong-Mahn HAN ,  Young-Ran KIM ,  Seulgi LEE

IPC: A61K31/52

CPC classification number: A61K31/52

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 translation: 本发明涉及一种预防和治疗源于对乙酰氨基酚的组合物，其包含TNP（N2-（间三氟苄基），N6-（对硝基苄基）嘌呤）作为活性成分。 本发明人证实，称为5-Inosito焦磷酸盐抑制剂的TNP抑制由人胚胎干细胞来源的肝细胞，小鼠肝细胞和人肝癌细胞系中的对乙酰氨基酚引起的凋亡，肝细胞中转化的上调的谷胱甘肽，并被抑制 对乙酰氨基酚增加的一种抗应激反应的JNK磷酸化。 本发明人进一步证实，TNP具有在动物模型中保护肝细胞免受对乙酰氨基酚引起的毒性的活性。 因此，TNP可以有效地用作预防和治疗由对乙酰氨基酚引起的肝毒性的组合物的活性成分。