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1. 发明申请

US20120028354A1 SYSTEMS AND METHODS FOR MAKING HEPATOCYTES FROM EXTRAHEPATIC SOMATIC STEM CELLS AND USE THEREOF 有权
标题翻译：用于从外来静脉干细胞制备肝细胞的系统和方法及其用途
公开(公告)号：US20120028354A1
公开(公告)日：2012-02-02
申请号：US13244411
申请日：2011-09-24
申请人： Oscar Kuang-Sheng LEE , Tom Kwang-Chun Kuo
发明人： Oscar Kuang-Sheng LEE , Tom Kwang-Chun Kuo
IPC分类号： C12N5/071
CPC分类号： G01N33/5067 , A61K35/407 , C12N5/067 , C12N2500/25 , C12N2500/38 , C12N2501/06 , C12N2501/113 , C12N2501/115 , C12N2501/119 , C12N2501/12 , C12N2501/155 , C12N2501/39 , C12N2503/02 , C12N2506/1353
摘要： A method for preparing isolated hepatocytes is disclosed. The method comprises: a) culturing mesenchymal stem cells (MSCs) in a medium comprising hepatic growth factor (HGF) to cause the MSCs to differentiate toward hepatocytes, wherein the MSCs are isolated from bone marrow or umbilical cord blood; b) culturing cells from a) in a medium comprising HGF and oncostatin M (OSM) to facilitate the cell differentiation toward hepatocytes; and c) culturing cells from b) in a medium comprising OSM to cause the differentiated cells to mature into hepatocytes, and thereby producing the isolated hepatocyte cells.
摘要翻译：公开了一种制备分离的肝细胞的方法。该方法包括：a）在包含肝细胞生长因子（HGF）的培养基中培养间充质干细胞（MSC）以使MSC分化为肝细胞，其中MSC从骨髓或脐带血分离; b）在包含HGF和制瘤素M（OSM）的培养基中培养来自a）的细胞，以促进细胞向肝细胞分化; 和c）在包含OSM的培养基中培养来自b）的细胞，使分化的细胞成熟为肝细胞，从而产生分离的肝细胞。

2. 发明申请

US20090317365A1 SYSTEMS AND METHODS FOR MAKING HEPATOCYTES FROM EXTRAHEPATIC SOMATIC STEM CELLS AND USE THEREOF 有权
标题翻译：用于从外来静脉干细胞制备肝细胞的系统和方法及其用途
公开(公告)号：US20090317365A1
公开(公告)日：2009-12-24
申请号：US12489760
申请日：2009-06-23
申请人： Oscar Kuang-Sheng LEE , Tom Kwang-Chun Kuo
发明人： Oscar Kuang-Sheng LEE , Tom Kwang-Chun Kuo
IPC分类号： A61K35/12 , C12N5/06 , C12Q1/02 , C12Q1/48 , C12Q1/42 , C12Q1/26
CPC分类号： G01N33/5067 , A61K35/407 , C12N5/067 , C12N2500/25 , C12N2500/38 , C12N2501/06 , C12N2501/113 , C12N2501/115 , C12N2501/119 , C12N2501/12 , C12N2501/155 , C12N2501/39 , C12N2503/02 , C12N2506/1353
摘要： A method for making hepatocytes from extrahepatic somatic stem cells comprises: a) culturing somatic stem cells in a medium comprising hepatic growth factor to cause the stem cells to differentiate toward hepatocytes; b) culturing cells from a) in a medium comprising HGF and oncostatin M to facilitate the cell differentiation toward hepatocytes; and c) culturing cells from b) in a medium comprising oncostatin M to cause the differentiated cells to mature into hepatocytes, thereby producing a cell population that has morphological features of hepatocytes and at least four of the following characteristics: i) antibody-detectable expression of albumin; ii) real-time reverse transcriptase-polymerase chain reaction-detectable expression of α-fetoprotein, HNF-1α, HNF-3β, HNF-4, HNF-6, α1-antitrypsin, alkaline phosphatase, tryptophan 2,3-dioxygenase, tyrosine aminotransferase, cytochrome P450 family 2 subfamily E polypeptide 1, glutamine synthetase, and/or low density lipoprotein receptor; iii) urea secretion; iv) cytochrome p450 enzyme activity; v) glycogen storage; and vi) low density lipoprotein uptake.
摘要翻译：从肝外体细胞干细胞制备肝细胞的方法包括：a）在包含肝细胞生长因子的培养基中培养体细胞干细胞，使干细胞分化成肝细胞; b）在包含HGF和制瘤素M的培养基中培养来自a）的细胞，以促进细胞向肝细胞分化; 和c）在包含制瘤素M的培养基中培养来自b）的细胞以使分化的细胞成熟为肝细胞，从而产生具有肝细胞形态特征和至少四种以下特征的细胞群：i）抗体可检测的表达白蛋白 ii）甲胎蛋白，HNF-1α，HNF-3β，HNF-4，HNF-6，α1-抗胰蛋白酶，碱性磷酸酶，色氨酸2,3-双加氧酶，酪氨酸的实时逆转录酶 - 聚合酶链反应可检测的表达氨基转移酶，细胞色素P450家族2亚科E多肽1，谷氨酰胺合成酶和/或低密度脂蛋白受体; iii）尿素分泌; iv）细胞色素p450酶活性; v）糖原储存; 和vi）低密度脂蛋白摄取。

3. 发明授权

US08216839B2 Systems and methods for making hepatocytes from extrahepatic somatic stem cells and use thereof 有权
标题翻译：用于从肝外体细胞干细胞制备肝细胞的系统和方法及其用途
公开(公告)号：US08216839B2
公开(公告)日：2012-07-10
申请号：US13244411
申请日：2011-09-24
申请人： Oscar Kuang-Sheng Lee , Tom Kwang-Chun Kuo
发明人： Oscar Kuang-Sheng Lee , Tom Kwang-Chun Kuo
IPC分类号： A01N63/00 , A01N65/00 , C12N5/00 , C12N5/02
CPC分类号： G01N33/5067 , A61K35/407 , C12N5/067 , C12N2500/25 , C12N2500/38 , C12N2501/06 , C12N2501/113 , C12N2501/115 , C12N2501/119 , C12N2501/12 , C12N2501/155 , C12N2501/39 , C12N2503/02 , C12N2506/1353
摘要： A method for preparing isolated hepatocytes is disclosed. The method comprises: a) culturing mesenchymal stem cells (MSCs) in a medium comprising hepatic growth factor (HGF) to cause the MSCs to differentiate toward hepatocytes, wherein the MSCs are isolated from bone marrow or umbilical cord blood; b) culturing cells from a) in a medium comprising HGF and oncostatin M (OSM) to facilitate the cell differentiation toward hepatocytes; and c) culturing cells from b) in a medium comprising OSM to cause the differentiated cells to mature into hepatocytes, and thereby producing the isolated hepatocyte cells.
摘要翻译：公开了一种制备分离的肝细胞的方法。该方法包括：a）在包含肝细胞生长因子（HGF）的培养基中培养间充质干细胞（MSC）以使MSC分化为肝细胞，其中MSC从骨髓或脐带血分离; b）在包含HGF和制瘤素M（OSM）的培养基中培养来自a）的细胞，以促进细胞向肝细胞分化; 和c）在包含OSM的培养基中培养来自b）的细胞，使分化的细胞成熟为肝细胞，从而产生分离的肝细胞。

4. 发明授权

US08062632B2 Systems and methods for making hepatocytes from extrahepatic somatic stem cells and use thereof 有权
标题翻译：用于从肝外体细胞干细胞制备肝细胞的系统和方法及其用途
公开(公告)号：US08062632B2
公开(公告)日：2011-11-22
申请号：US12489760
申请日：2009-06-23
申请人： Oscar Kuang-Sheng Lee , Tom Kwang-Chun Kuo
发明人： Oscar Kuang-Sheng Lee , Tom Kwang-Chun Kuo
IPC分类号： A01N63/00 , A01N65/00
CPC分类号： G01N33/5067 , A61K35/407 , C12N5/067 , C12N2500/25 , C12N2500/38 , C12N2501/06 , C12N2501/113 , C12N2501/115 , C12N2501/119 , C12N2501/12 , C12N2501/155 , C12N2501/39 , C12N2503/02 , C12N2506/1353
摘要： A method for making hepatocytes from extrahepatic somatic stem cells comprises: a) culturing somatic stem cells in a medium comprising hepatic growth factor to cause the stem cells to differentiate toward hepatocytes; b) culturing cells from a) in a medium comprising HGF and oncostatin M to facilitate the cell differentiation toward hepatocytes; and c) culturing cells from b) in a medium comprising oncostatin M to cause the differentiated cells to mature into hepatocytes, thereby producing a cell population that has morphological features of hepatocytes and at least four of the following characteristics: i) antibody-detectable expression of albumin; ii) real-time reverse transcriptase-polymerase chain reaction-detectable expression of α-fetoprotein, HNF-1α, HNF-3β, HNF-4, HNF-6, α1-antitrypsin, alkaline phosphatase, tryptophan 2,3-dioxygenase, tyrosine aminotransferase, cytochrome P450 family 2 subfamily E polypeptide 1, glutamine synthetase, and/or low density lipoprotein receptor; iii) urea secretion; iv) cytochrome p450 enzyme activity; v) glycogen storage; and vi) low density lipoprotein uptake.
摘要翻译：从肝外体细胞干细胞制备肝细胞的方法包括：a）在包含肝细胞生长因子的培养基中培养体细胞干细胞，使干细胞分化成肝细胞; b）在包含HGF和制瘤素M的培养基中培养来自a）的细胞，以促进细胞向肝细胞分化; 和c）在包含制瘤素M的培养基中培养来自b）的细胞以使分化的细胞成熟为肝细胞，从而产生具有肝细胞形态特征和至少四种以下特征的细胞群：i）抗体可检测的表达白蛋白 ii）甲胎蛋白，HNF-1α，HNF-3和bgr，HNF-4，HNF-6，α1-抗胰蛋白酶，碱性磷酸酶，色氨酸2,3-双加氧酶，实时逆转录酶 - 聚合酶链反应检测的表达，酪氨酸氨基转移酶，细胞色素P450家族2亚家族E多肽1，谷氨酰胺合成酶和/或低密度脂蛋白受体; iii）尿素分泌; iv）细胞色素p450酶活性; v）糖原储存; 和vi）低密度脂蛋白摄取。

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