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1. 发明授权

US08691523B2 Primitive and proximal hepatic stem cells 有权
标题翻译：原始和近端肝干细胞
公开(公告)号：US08691523B2
公开(公告)日：2014-04-08
申请号：US11609729
申请日：2006-12-12
申请人： Lola M. Reid , Nicholas Moss , Mark E. Furth , John W. Ludlow , Andrew T. Bruce
发明人： Lola M. Reid , Nicholas Moss , Mark E. Furth , John W. Ludlow , Andrew T. Bruce
IPC分类号： C12N5/00
CPC分类号： C12N5/0672 , C12N2500/25 , C12N2500/36 , C12N2500/90 , C12N2501/11 , C12N2502/13 , G01N33/5005 , G01N33/68 , G01N2333/705 , G01N2333/70525 , G01N2333/70596
摘要： 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.
摘要翻译：肝祖细胞包含两个人类肝干细胞，原始和近端肝干细胞，以及两个定型祖细胞群，一个为胆汁细胞，一个为肝细胞。人原始肝干细胞是肝细胞群体的非常小的一部分，并且引起近端肝干细胞构成肝脏的大部分。人近端肝干细胞产生胆汁和肝细胞定向的祖细胞。原始和近端干细胞是人类肝脏的主要干细胞。人原始肝干细胞可以通过人肝脏的免疫选择或在选择人原始肝干细胞的条件下培养人肝细胞来分离。可以通过免疫选择或通过在包括发育因子的条件下培养人肝细胞来分离近端肝干细胞。也可以通过在包括发育因子的条件下培养包含原始肝干细胞的菌落来分离近端肝干细胞。所得组合物可用于治疗肝脏疾病和用于生产生物人造器官。

2. 发明申请

US20100112689A1 METHOD OF OBTAINING VIABLE HUMAN CELLS, INCLUDING HEPATIC STEM/PROGENITOR CELLS 审中-公开
标题翻译：获得可行的人类细胞的方法，包括HEPATIC STEM / PROGENITOR CELLS
公开(公告)号：US20100112689A1
公开(公告)日：2010-05-06
申请号：US12465404
申请日：2009-05-13
申请人： John W. Ludlow , Mark E. Furth , Andrew T. Bruce , Lola M. Reid , Robert L. Susick, JR.
发明人： John W. Ludlow , Mark E. Furth , Andrew T. Bruce , Lola M. Reid , Robert L. Susick, JR.
IPC分类号： C12N5/071
CPC分类号： C12N5/067 , C12N2509/00
摘要： The present invention is directed toward a method for obtaining from whole liver or a resection thereof a population of cells comprising viable, functional liver cells enriched in hepatocytes and hepatocyte stem/progenitor cells, compositions thereof, and uses therefore. Compositions include a composition of liver cells enriched in hepatocytes and hepatocyte stem/progenitor cells and a pharmaceutical composition thereof. Uses include treatment of liver diseases, regeneration of liver, toxicity testing, and liver assist devices.
摘要翻译：本发明涉及从整个肝脏或其切除方法获得包含富含肝细胞的活的功能性肝细胞和肝细胞干细胞/祖细胞的细胞群，以及其组合物及其用途。组合物包括富含肝细胞的肝细胞和肝细胞干/祖细胞的组合物及其药物组合物。用途包括肝脏疾病的治疗，肝脏再生，毒性试验和肝脏辅助装置。

3. 发明授权

US07413897B2 Primitive and proximal hepatic stem cells 有权
标题翻译：原始和近端肝干细胞
公开(公告)号：US07413897B2
公开(公告)日：2008-08-19
申请号：US10387547
申请日：2003-03-14
申请人： Lola M. Reid , Nicholas Moss , Mark Furth , John W. Ludlow , Andrew T. Bruce
发明人： Lola M. Reid , Nicholas Moss , Mark Furth , John W. Ludlow , Andrew T. Bruce
IPC分类号： C12N5/00 , A01N63/00
CPC分类号： C12N5/0672 , C12N2500/25 , C12N2500/36 , C12N2500/90 , C12N2501/11 , C12N2502/13 , G01N33/5005 , G01N33/68 , G01N2333/705 , G01N2333/70525 , G01N2333/70596
摘要： 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.
摘要翻译：肝祖细胞包含两个人类肝干细胞，原始和近端肝干细胞，以及两个定型祖细胞群，一个为胆汁细胞，一个为肝细胞。人原始肝干细胞是肝细胞群体的非常小的一部分，并且引起近端肝干细胞构成肝脏的大部分。人近端肝干细胞产生胆汁和肝细胞定向的祖细胞。原始和近端干细胞是人类肝脏的主要干细胞。人原始肝干细胞可以通过人肝脏的免疫选择或在选择人原始肝干细胞的条件下培养人肝细胞来分离。可以通过免疫选择或通过在包括发育因子的条件下培养人肝细胞来分离近端肝干细胞。也可以通过在包括发育因子的条件下培养包含原始肝干细胞的菌落来分离近端肝干细胞。所得组合物可用于治疗肝脏疾病和用于生产生物人造器官。

4. 发明申请

US20100197015A1 HUMAN LIVER PROGENITORS 审中-公开
标题翻译：人类生殖器
公开(公告)号：US20100197015A1
公开(公告)日：2010-08-05
申请号：US12695855
申请日：2010-01-28
申请人： Lola M. Reid , Nicholas Moss , Hiroshi Kubota
发明人： Lola M. Reid , Nicholas Moss , Hiroshi Kubota
IPC分类号： C12N5/071
CPC分类号： C12N5/0672 , A61K35/12 , A61K2039/55594 , C12N2500/20 , C12N2500/22 , C12N2500/25 , C12N2500/36 , C12N2503/02
摘要： Methods of isolating and cryopreserving progenitors from human liver are disclosed which include processing human liver tissue to provide a substantially single cell suspension comprising progenitors and non-progenitors of one or more cell lineages found in human liver; subjecting the suspension to a debulking step, which reduces substantially the number of non-progenitors in the suspension, and which provides a debulked suspension enriched in progenitors exhibiting one or more markers associated with at least one of the one or more cell lineages; and selecting from said debulked suspension those cells, which themselves, their progeny, or more mature forms thereof express one or more markers associated with at least one of the one or more cell lineages. Among these markers are CD14, CD34, CD38, CD45, and ICAM. Hepatic progenitors are characterized as being 6-15μ in diameter, diploid, glycophorin A−, CD45−, AFP+++, ALB+, ICAM+, and with subpopulations varying in expression of CD14+. CD34++, CD38++, CD117+. These progenitor subpopulations have characteristics expected for cells that are particularly useful in liver cell and gene therapies and for establishing bioartificial organs.
摘要翻译：公开了从人肝脏分离和冷冻保存祖细胞的方法，其包括加工人肝组织以提供包含在人肝脏中发现的一种或多种细胞谱系的祖细胞和非祖细胞的基本上单细胞悬浮液; 使悬浮液经历减压步骤，其减少了悬浮液中的非祖细胞的数量，并且提供了富含前体细胞的减数分裂的悬浮液，其显示出与一种或多种细胞系中的至少一种相关联的一种或多种标志物; 以及从所述减粘悬浮液中选择这些细胞，其本身，其子代或更成熟的形式表达与所述一种或多种细胞谱系中的至少一种相关联的一种或多种标志物。这些标记物中有CD14，CD34，CD38，CD45和ICAM。肝祖细胞的特征是直径为6-15μ，二倍体，血型糖蛋白A-，CD45-，AFP +++，ALB +，ICAM +，以及与CD14 +表达不同的亚群。 CD34 ++，CD38 ++，CD117 +。这些祖细胞亚群具有特别适用于肝细胞和基因疗法以及建立生物人造器官的细胞的特征。

5. 发明申请

US20130071834A1 COMPOSITIONS AND METHODS USEFUL FOR HCV INFECTION 审中-公开
标题翻译：用于HCV感染的组合物和方法
公开(公告)号：US20130071834A1
公开(公告)日：2013-03-21
申请号：US13538777
申请日：2012-06-29
申请人： Ann Kwong , Randal Byrn , Lola M. Reid
发明人： Ann Kwong , Randal Byrn , Lola M. Reid
IPC分类号： C12Q1/70 , C12N5/071 , C12N5/00
CPC分类号： C12Q1/70 , C12N5/0031 , C12N5/0037 , C12N5/067 , C12N7/00 , C12N2500/20 , C12N2500/25 , C12N2500/36 , C12N2500/46 , C12N2500/90 , C12N2501/11 , C12N2501/12 , C12N2501/18 , C12N2501/335 , C12N2501/375 , C12N2501/39 , C12N2502/11 , C12N2770/24011
摘要： The present invention provides compositions comprising cells that can effectively produce HCV after HCV infection, compositions for culturing the cells, methods for making the composition and methods for infecting the cells in the composition with HCV. The present invention also provides methods for assaying HCV production and methods for evaluating compounds that affect the production of HCV.
摘要翻译：本发明提供包含可以在HCV感染后有效产生HCV的细胞的组合物，用于培养细胞的组合物，用于制备组合物的方法和用HCV感染组合物中的细胞的方法。本发明还提供了用于测定HCV产生的方法以及评价影响HCV产生的化合物的方法。

6. 发明申请

US20110065188A1 Paracrine signals from mesenchymal feeder cells and regulating expansion and differentiation of hepatic progenitors using same 失效
标题翻译：旁分泌信号来自间充质细胞，调节肝祖细胞的扩增和分化
公开(公告)号：US20110065188A1
公开(公告)日：2011-03-17
申请号：US12923253
申请日：2010-09-10
申请人： Lola M. Reid , Randall E. Mcclelland , Joshua Uronis , Hsin-Lei Yao , Eliane Wauthier
发明人： Lola M. Reid , Randall E. Mcclelland , Joshua Uronis , Hsin-Lei Yao , Eliane Wauthier
IPC分类号： C12N5/071 , C12M3/00
CPC分类号： C12N5/0672 , C12N2502/13 , C12N2533/52 , C12N2533/54 , C12N2533/80
摘要： A method is provided for controlling the survival, proliferation, and/or differentiation of hepatic progenitors in vitro by using specific types of mesenchymal feeder cells or one of more of the paracrine signals produced by those feeders.
摘要翻译：提供了一种通过使用特定类型的间充质细胞或由这些饲养者产生的更多的旁分泌信号之一来控制肝祖细胞的存活，增殖和/或分化的方法。

7. 发明授权

US08691579B2 Methods of isolating bipotent hepatic progenitor cells 有权
标题翻译：分离双能肝祖细胞的方法
公开(公告)号：US08691579B2
公开(公告)日：2014-04-08
申请号：US12326514
申请日：2008-12-02
申请人： Hiroshi Kubota , Lola M. Reid
发明人： Hiroshi Kubota , Lola M. Reid
IPC分类号： C12N15/09 , C12N5/00
CPC分类号： G01N33/5091 , C12N5/0672 , C12N2501/50 , C12N2501/58 , C12N2501/599
摘要： A method of obtaining a mixture of cells enriched in hepatic progenitors is developed which comprises methods yielding suspensions of a mixture of cell types, and selecting those cells that are classical MHC class I antigen(s) negative and ICAM-1 antigen positive. The weak or dull expression of nonclassical MHC class I antigen(s) can be used for further enrichment of hepatic progenitors. Furthermore, the progenitors can be selected to have a level of side scatter, a measure of granularity or cytoplasmic droplets, that is higher than that in non-parenchymal cells, such as hemopoietic cells, and lower than that in mature parenchymal cells, such as hepatocytes. Furthermore, the progeny of the isolated progenitors can express alpha-fetoprotein and/or albumin and/or CK19. The hepatic progenitors, so isolated, can grow clonally, that is an entire population of progeny can be derived from one cell. The clones of progenitors have a growth pattern in culture of piled-up aggregates or clusters. These methods of isolating the hepatic progenitors are applicable to any vertebrates including human. The hepatic progenitor cell population is expected to be useful for cell therapies, for bioartificial livers, for gene therapies, for vaccine development, and for myriad toxicological, pharmacological, and pharmaceutical programs and investigations.
摘要翻译：开发了获得富含肝祖细胞的细胞混合物的方法，其包括产生细胞类型混合物的悬浮液的方法，并选择那些经典的MHC I类抗原和ICAM-1抗原阳性的细胞。非典型MHC I类抗原的弱或暗的表达可用于进一步富集肝祖细胞。此外，可以选择祖细胞具有高于非实质细胞例如造血细胞的侧向散射，粒度或细胞质液滴的量级，并且低于成熟实质细胞中的祖细胞，例如肝细胞。此外，分离的祖细胞的后代可以表达甲胎蛋白和/或白蛋白和/或CK19。如此分离的肝祖细胞可以克隆生长，即可以从一个细胞中获得后代的全部群体。祖先的克隆在堆积聚集体或簇的培养中具有增长模式。这些分离肝祖细胞的方法适用于包括人在内的任何脊椎动物。预期肝祖细胞群可用于细胞疗法，生物人工肝，基因治疗，疫苗开发和无数毒理学，药理学和药物程序和调查。

8. 发明申请

US20120028353A1 HEPATIC STELLATE CELL PRECURSORS AND METHODS OF ISOLATING SAME 审中-公开
标题翻译： HEPATIC STELLATE CELL PRECURSORS和隔离方法
公开(公告)号：US20120028353A1
公开(公告)日：2012-02-02
申请号：US12903824
申请日：2010-10-13
申请人： Hiroshi Kubota , Lola M. Reid
发明人： Hiroshi Kubota , Lola M. Reid
IPC分类号： C12N5/071
CPC分类号： C12N5/0018 , C12N5/067 , C12N5/0672 , C12N2500/00 , C12N2500/05 , C12N2500/20 , C12N2500/25 , C12N2500/32 , C12N2500/36 , C12N2500/38 , C12N2500/90 , C12N2501/00 , C12N2501/11 , C12N2501/235 , C12N2501/33 , G01N33/56966
摘要： The present invention relates to precursor cells to hepatic stellate cells, compositions comprising same and methods of isolating same. The surface antigenic profile of the precursors is MHC class Ia negative, ICAM-1+, VCAM-1+, β3-integrin+. In addition to expression of these surface markers, the cells also express the intracellular markers desmin, vimentin, smooth muscle α-actin, nestin, hepatocyte growth factor, stromal derived factor-1α and Hlx homeobox transcriptional factor.
摘要翻译：本发明涉及肝星状细胞的前体细胞，包含其的组合物及其分离方法。前体的表面抗原谱是MHC Ia类阴性，ICAM-1 +，VCAM-1 +，＆bgr。3-整联蛋白+。除了这些表面标志物的表达外，细胞还表达细胞内标志物结蛋白，波形蛋白，平滑肌α-肌动蛋白，巢蛋白，肝细胞生长因子，基质衍生因子-1α和Hlx同源异位转录因子。

9. 发明申请

US20110229874A1 COMPOSITIONS AND METHODS USEFUL FOR HCV INFECTION 失效
标题翻译：用于HCV感染的组合物和方法
公开(公告)号：US20110229874A1
公开(公告)日：2011-09-22
申请号：US13013758
申请日：2011-01-25
申请人： Ann Kwong , Randal Byrn , Lola M. Reid
发明人： Ann Kwong , Randal Byrn , Lola M. Reid
IPC分类号： C12Q1/70 , C12N5/078 , C12N7/00
CPC分类号： C12Q1/70 , C12N5/0031 , C12N5/0037 , C12N5/067 , C12N7/00 , C12N2500/20 , C12N2500/25 , C12N2500/36 , C12N2500/46 , C12N2500/90 , C12N2501/11 , C12N2501/12 , C12N2501/18 , C12N2501/335 , C12N2501/375 , C12N2501/39 , C12N2502/11 , C12N2770/24011
摘要： The present invention provides compositions comprising cells that can effectively produce HCV after HCV infection, compositions for culturing the cells, methods for making the composition and methods for infecting the cells in the composition with HCV. The present invention also provides methods for assaying HCV production and methods for evaluating compounds that affect the production of HCV.
摘要翻译：本发明提供包含可以在HCV感染后有效产生HCV的细胞的组合物，用于培养细胞的组合物，用于制备组合物的方法和用HCV感染组合物中的细胞的方法。本发明还提供了用于测定HCV产生的方法以及评价影响HCV产生的化合物的方法。

10. 发明授权

US06242252B1 Hepatic progenitors and method of isolating same 有权
标题翻译：肝祖细胞及其分离方法
公开(公告)号：US06242252B1
公开(公告)日：2001-06-05
申请号：US09154222
申请日：1998-09-16
申请人： Lola M. Reid , Samuel H. Sigal , Shlomo Brill , Patricia A. Holst
发明人： Lola M. Reid , Samuel H. Sigal , Shlomo Brill , Patricia A. Holst
IPC分类号： C12N500
CPC分类号： C12N5/0068 , A61K35/12 , C12N5/0672 , C12N2500/20 , C12N2500/22 , C12N2500/25 , C12N2500/36 , C12N2500/90 , C12N2501/11 , C12N2501/305 , C12N2501/315 , C12N2501/39 , C12N2501/395 , C12N2509/00 , C12N2510/00 , G01N33/5017 , G01N33/57438
摘要： This invention relates to methods of isolating hepatic progenitors utilizing panning techniques and fluorescence activated cell sorting. This invention further relates to isolated hepatic progenitors and to a method of treating liver dysfunction as well as to methods of forming artificial livers.
摘要翻译：本发明涉及利用淘选技术和荧光激活细胞分选来分离肝祖细胞的方法。本发明还涉及分离的肝祖细胞和治疗肝功能障碍的方法以及形成人肝的方法。

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