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1. 发明授权

US07897389B2 Direct differentiation method for making cardiomyocytes from human embryonic stem cells 有权
标题翻译：用于从人类胚胎干细胞制备心肌细胞的直接分化方法
公开(公告)号：US07897389B2
公开(公告)日：2011-03-01
申请号：US12210779
申请日：2008-09-15
申请人： Joseph D. Gold , Mohammad Hassanipour , Lila R. Collins , Chunhui Xu
发明人： Joseph D. Gold , Mohammad Hassanipour , Lila R. Collins , Chunhui Xu
IPC分类号： C12N5/00 , C12N5/02 , C12N5/07 , C12N5/10
CPC分类号： C12N5/0657 , C12N2500/25 , C12N2500/90 , C12N2501/155 , C12N2501/16 , C12N2506/02
摘要： This invention provides a new procedure for generating cardiomyocyte lineage cells from embryonic stem cells for use in regenerative medicine. Differentiating by way of embryoid body formation or in serum is no longer required. Instead, the stem cells are plated onto a solid substrate, and differentiated in the presence of select factors and morphogens. After enrichment for cells with the appropriate phenotype, the cells are allowed to cluster into Cardiac Bodies™, which are remarkably homogeneous and suitable for the treatment of heart disease.
摘要翻译：本发明提供了用于从再生医学中使用的胚胎干细胞产生心肌细胞谱系细胞的新方法。不再需要通过胚状体形成或血清分化。相反，将干细胞铺在固体底物上，并在存在选择因子和形态发生的情况下分化。在具有适当表型的细胞富集后，允许细胞聚集到心脏体TM中，其是非常均匀的并且适合于治疗心脏病。

2. 发明授权

US07452718B2 Direct differentiation method for making cardiomyocytes from human embryonic stem cells 有权
标题翻译：用于从人类胚胎干细胞制备心肌细胞的直接分化方法
公开(公告)号：US07452718B2
公开(公告)日：2008-11-18
申请号：US11086709
申请日：2005-03-21
申请人： Joseph D. Gold , Mohammad Hassanipour , Lila R. Collins , Chunhui Xu
发明人： Joseph D. Gold , Mohammad Hassanipour , Lila R. Collins , Chunhui Xu
IPC分类号： C12N5/00 , C12N5/02 , C12N5/06 , C12N5/10 , C12N5/08
CPC分类号： C12N5/0657 , C12N2500/25 , C12N2500/90 , C12N2501/155 , C12N2501/16 , C12N2506/02
摘要： This invention provides a new procedure for generating cardiomyocyte lineage cells from embryonic stem cells for use in regenerative medicine. Differentiating by way of embryoid body formation or in serum is no longer required. Instead, the stem cells are plated onto a solid substrate, and differentiated in the presence of select factors and morphogens. After enrichment for cells with the appropriate phenotype, the cells are allowed to cluster into cardiac bodies™, which are remarkably homogeneous and suitable for the treatment of heart disease.
摘要翻译：本发明提供了用于从再生医学中使用的胚胎干细胞产生心肌细胞谱系细胞的新方法。不再需要通过胚状体形成或血清分化。相反，将干细胞铺在固体底物上，并在存在选择因子和形态发生的情况下分化。在具有适当表型的细胞富集后，允许细胞聚集到心脏体（TM）中，其是非常均匀的并且适合于治疗心脏病。

3. 发明授权

US10059939B2 Screening methods for human embryonic stem cells 有权
公开(公告)号：US10059939B2
公开(公告)日：2018-08-28
申请号：US13323567
申请日：2011-12-12
申请人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
发明人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
IPC分类号： C12N15/10 , C12N5/0735 , C12N5/079 , C12N5/0793 , C12N5/074 , C12N5/00 , C12N5/071 , C12N11/04 , C12N5/073 , C12N5/09 , C12N5/0775
CPC分类号： C12N15/1096 , C12N5/0062 , C12N5/0068 , C12N5/0075 , C12N5/0603 , C12N5/0606 , C12N5/0607 , C12N5/0619 , C12N5/0622 , C12N5/0662 , C12N5/0671 , C12N5/0672 , C12N5/0678 , C12N5/068 , C12N5/0692 , C12N5/0693 , C12N5/0696 , C12N11/04 , C12N15/1034 , C12N2500/25 , C12N2500/90 , C12N2500/98 , C12N2500/99 , C12N2501/065 , C12N2501/105 , C12N2501/115 , C12N2501/119 , C12N2501/125 , C12N2501/13 , C12N2501/145 , C12N2501/155 , C12N2501/2306 , C12N2501/235 , C12N2501/237 , C12N2501/26 , C12N2501/998 , C12N2502/13 , C12N2502/99 , C12N2503/02 , C12N2506/02 , C12N2510/00 , C12N2510/04 , C12N2533/50 , C12N2533/90
摘要： This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.

4. 发明申请

US20140302600A9 PRIMATE PLURIPOTENT STEM CELL EXPANSION WITHOUT FEEDER CELLS AND IN THE PRESENCE OF FGF AND MATRIGEL OR ENGELBRETH-HOLM-SWARM TUMOR CELL PREAPARATION 有权
标题翻译：在没有饲养细胞的情况下，在FGF和矩阵或恩格列酮 - 耳膜 - 肿瘤肿瘤细胞预先存在的情况下，初始细胞干细胞扩增
公开(公告)号：US20140302600A9
公开(公告)日：2014-10-09
申请号：US12710078
申请日：2010-02-22
申请人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
发明人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
IPC分类号： C12N5/074
CPC分类号： C12N15/1096 , C12N5/0062 , C12N5/0068 , C12N5/0075 , C12N5/0603 , C12N5/0606 , C12N5/0607 , C12N5/0619 , C12N5/0622 , C12N5/0662 , C12N5/0671 , C12N5/0672 , C12N5/0678 , C12N5/068 , C12N5/0692 , C12N5/0693 , C12N5/0696 , C12N11/04 , C12N15/1034 , C12N2500/25 , C12N2500/90 , C12N2500/98 , C12N2500/99 , C12N2501/065 , C12N2501/105 , C12N2501/115 , C12N2501/119 , C12N2501/125 , C12N2501/13 , C12N2501/145 , C12N2501/155 , C12N2501/2306 , C12N2501/235 , C12N2501/237 , C12N2501/26 , C12N2501/998 , C12N2502/13 , C12N2502/99 , C12N2503/02 , C12N2506/02 , C12N2510/00 , C12N2510/04 , C12N2533/50 , C12N2533/90
摘要： This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
摘要翻译：本公开提供了一种用于培养人多能干细胞的改进系统。传统上，多能干细胞在一层饲养细胞（如小鼠胚胎成纤维细胞）上培养以防止它们分化。在这里描述的系统中，饲养细胞的作用由添加到培养环境中的组分代替，其支持快速增殖而不分化。有效的特征是细胞的合适的支持结构，以及可以在不被另一种细胞类型预处理的情况下可以新鲜添加到培养物中的有效培养基。在根据本发明的新鲜培养基中培养人胚胎干细胞导致细胞惊人地快速扩张，同时保持分化成代表所有三个胚胎胚层的细胞的能力。这种新的培养系统允许pPS细胞的大量增殖用于商业生产用于药物筛选和人类治疗的重要产品。

5. 发明授权

US08426198B2 In vitro differentiated cell and human embryonic stem cell population 有权
标题翻译：体外分化细胞和人胚胎干细胞群体
公开(公告)号：US08426198B2
公开(公告)日：2013-04-23
申请号：US11359341
申请日：2006-02-21
申请人： Joseph D. Gold , Jane S. Lebkowski
发明人： Joseph D. Gold , Jane S. Lebkowski
IPC分类号： C12N5/071 , C12N15/00
CPC分类号： C12N15/85 , A61K35/12 , C12N5/0606 , C12N2502/13 , C12N2510/00
摘要： This invention provides a system for producing differentiated cells from a stem cell population for use wherever a relatively homogenous cell population is desirable. The cells contain an effector gene under control of a transcriptional control element (such as the TERT promoter) that causes the gene to be expressed in relatively undifferentiated cells in the population. Expression of the effector gene results in depletion of undifferentiated cells, or expression of a marker that can be used to remove them later. Suitable effector sequences encode a toxin, a protein that induces apoptosis; a cell-surface antigen, or an enzyme (such as thymidine kinase) that converts a prodrug into a substance that is lethal to the cell. The differentiated cell populations produced according to this disclosure are suitable for use in tissue regeneration, and non-therapeutic applications such as drug screening.
摘要翻译：本发明提供了一种用于从干细胞群体产生分化细胞的系统，用于需要相对均匀细胞群体的地方。细胞含有在转录控制元件（例如TERT启动子）的控制下的效应基因，其导致基因在群体中相对未分化的细胞中表达。效应基因的表达导致未分化细胞的消耗或可以用于稍后去除它们的标记物的表达。合适的效应序列编码毒素，诱导细胞凋亡的蛋白质; 细胞表面抗原或将前药转化为对细胞致死的物质的酶（例如胸苷激酶）。根据本公开生产的分化细胞群体适用于组织再生和非治疗应用，例如药物筛选。

6. 发明申请

US20100317101A1 Culture System for Rapid Expansion of Human Embryonic Stem Cells 有权
标题翻译：人类胚胎干细胞快速扩增培养体系
公开(公告)号：US20100317101A1
公开(公告)日：2010-12-16
申请号：US12710078
申请日：2010-02-22
申请人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
发明人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
IPC分类号： C12N5/074
CPC分类号： C12N15/1096 , C12N5/0062 , C12N5/0068 , C12N5/0075 , C12N5/0603 , C12N5/0606 , C12N5/0607 , C12N5/0619 , C12N5/0622 , C12N5/0662 , C12N5/0671 , C12N5/0672 , C12N5/0678 , C12N5/068 , C12N5/0692 , C12N5/0693 , C12N5/0696 , C12N11/04 , C12N15/1034 , C12N2500/25 , C12N2500/90 , C12N2500/98 , C12N2500/99 , C12N2501/065 , C12N2501/105 , C12N2501/115 , C12N2501/119 , C12N2501/125 , C12N2501/13 , C12N2501/145 , C12N2501/155 , C12N2501/2306 , C12N2501/235 , C12N2501/237 , C12N2501/26 , C12N2501/998 , C12N2502/13 , C12N2502/99 , C12N2503/02 , C12N2506/02 , C12N2510/00 , C12N2510/04 , C12N2533/50 , C12N2533/90
摘要： This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
摘要翻译：本公开提供了一种用于培养人多能干细胞的改进系统。传统上，多能干细胞在一层饲养细胞（如小鼠胚胎成纤维细胞）上培养以防止它们分化。在这里描述的系统中，饲养细胞的作用由添加到培养环境中的组分代替，其支持快速增殖而不分化。有效的特征是细胞的合适的支持结构，以及可以在不被另一种细胞类型预处理的情况下可以新鲜添加到培养物中的有效培养基。在根据本发明的新鲜培养基中培养人胚胎干细胞导致细胞惊人地快速扩张，同时保持分化成代表所有三个胚胎胚层的细胞的能力。这种新的培养系统允许pPS细胞的大量增殖用于商业生产用于药物筛选和人类治疗的重要产品。

7. 发明申请

US20090263835A1 Genes that are Up- or Down-Regulated During Differentiation of Human Embryonic Stem Cells 审中-公开
标题翻译：在人类胚胎干细胞分化过程中上调或下调的基因
公开(公告)号：US20090263835A1
公开(公告)日：2009-10-22
申请号：US12487869
申请日：2009-06-19
申请人： Lawrence W. Stanton , Ralph Brandenberger , Joseph D. Gold , John M. Irving , Ramkumar Mandalam , Michael Mok , Dawne Shelton
发明人： Lawrence W. Stanton , Ralph Brandenberger , Joseph D. Gold , John M. Irving , Ramkumar Mandalam , Michael Mok , Dawne Shelton
IPC分类号： G01N33/53
CPC分类号： C12Q1/6876 , C12Q1/68 , C12Q1/6886 , C12Q2600/158
摘要： Genes that are up- or down-regulated during differentiation provide important leverage by which to characterize and manipulate early-stage pluripotent stem cells. Over 35,000 unique transcripts have been amplified and sequenced from undifferentiated human embryonic stem cells, and three types of differentiated progeny. Statistical analysis of the assembled transcripts identified genes that alter expression levels as differentiation proceeds. The expression profile provides a marker system that has been used to identify particular culture components for maintaining the undifferentiated phenotype. The gene products can also be used to promote differentiation; to assess other relatively undifferentiated cells (such as cancer cells); to control gene expression; or to separate cells having desirable characteristics. Manipulation of particular genes can be used to forestall or focus the differentiation process, en route to producing a specialized homogenous cell population suitable for human therapy.
摘要翻译：在分化期间上调或下调的基因提供了表征和操纵早期多能干细胞的重要作用。已经从未分化的人类胚胎干细胞和三种类型的分化后代中扩增和测序了超过35,000个独特的转录物。组装的转录物的统计分析确定了在分化进行时改变表达水平的基因。表达谱提供了用于鉴定用于维持未分化表型的特定培养组分的标记系统。基因产物也可用于促进分化; 评估其他相对未分化的细胞（如癌细胞）; 控制基因表达; 或分离具有所需特征的细胞。特定基因的操作可用于预防或集中分化过程，途径是产生适合人类治疗的专门的均质细胞群。

8. 发明授权

US06800480B1 Methods and materials for the growth of primate-derived primordial stem cells in feeder-free culture 有权
标题翻译：用于无饲养细胞培养的灵长类动物原始干细胞生长的方法和材料
公开(公告)号：US06800480B1
公开(公告)日：2004-10-05
申请号：US09530346
申请日：2000-08-29
申请人： Andrea G. Bodnar , Choy-Pik Chiu , Joseph D. Gold , Margaret Inokuma , James T. Murai , Michael D. West
发明人： Andrea G. Bodnar , Choy-Pik Chiu , Joseph D. Gold , Margaret Inokuma , James T. Murai , Michael D. West
IPC分类号： C12N500
CPC分类号： C12N5/0606 , C12N2500/40 , C12N2500/44 , C12N2501/385 , C12N2502/13 , C12N2510/00
摘要： Methods and materials for culturing primate-derived primordial stem cells are described. In one embodiment, a cell culture medium for growing primate-derived primordial stem cells in a substantially undifferentiated state is provided which includes a low osmotic pressure, low endotoxin basic medium that is effective to support the growth of primate-derived primordial stem cells. The basic medium is combined with a nutrient serum effective to support the growth of primate-derived primordial stem cells and a substrate selected from the group consisting of feeder cells and an extracellular matrix component derived from feeder cells. The medium further includes non-essential amino acids, an anti-oxidant, and a first growth factor selected from the group consisting of nucleosides and a pyruvate salt.
摘要翻译：描述了用于培养灵长类衍生的原始干细胞的方法和材料。在一个实施方案中，提供了用于生长基本上未分化状态的灵长类来源的原始干细胞的细胞培养基，其包括低渗透压，有效支持灵长类来源的原始干细胞的生长的低内毒素碱性培养基。基本培养基与有效支持灵长类衍生的原始干细胞的生长的营养血清和选自饲养细胞和源自饲养细胞的细胞外基质组分的底物组合。该培养基还包括非必需氨基酸，抗氧化剂和选自核苷和丙酮酸盐的第一生长因子。

9. 发明授权

US09062289B2 Differentiation of primate pluripotent stem cells to cardiomyocyte-lineage cells 有权
标题翻译：灵长类动物多能干细胞分化为心肌细胞谱系细胞
公开(公告)号：US09062289B2
公开(公告)日：2015-06-23
申请号：US11471916
申请日：2006-06-20
申请人： Joseph D. Gold , Mohammad Hassanipour
发明人： Joseph D. Gold , Mohammad Hassanipour
IPC分类号： C12N5/00 , C12N5/077
CPC分类号： C12N5/0657 , C12N2500/90 , C12N2501/105 , C12N2501/155 , C12N2501/16 , C12N2506/02 , C12N2533/54
摘要： The present application describes the new methods for the differentiation of primate pluripotent stem cells into cardiomyocyte-lineage cells. The methods utilize sequential culturing of the primate pluripotent stem cells in certain growth factors to produce cardiomyocyte-lineage cells. In certain embodiments of the invention, the population of cells produced by the sequential culturing is further enriched for cardiomyocyte-lineage cells so as to produce a higher percentage of those cells.
摘要翻译：本申请描述了将灵长动物多能干细胞分化为心肌细胞谱系细胞的新方法。该方法利用灵长动物多能干细胞在某些生长因子中的顺序培养来产生心肌细胞谱系细胞。在本发明的某些实施方案中，通过顺序培养产生的细胞群进一步富集心肌细胞谱系细胞，从而产生较高百分比的这些细胞。

10. 发明申请

US20120149025A1 Screening Methods for Human Embryonic Stem Cells 审中-公开
标题翻译：人类胚胎干细胞的筛选方法
公开(公告)号：US20120149025A1
公开(公告)日：2012-06-14
申请号：US13323567
申请日：2011-12-12
申请人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
发明人： Ramkumar Mandalam , Chunhui Xu , Joseph D. Gold , Melissa K. Carpenter
IPC分类号： C12Q1/68 , G01N33/566 , C12Q1/02
CPC分类号： C12N15/1096 , C12N5/0062 , C12N5/0068 , C12N5/0075 , C12N5/0603 , C12N5/0606 , C12N5/0607 , C12N5/0619 , C12N5/0622 , C12N5/0662 , C12N5/0671 , C12N5/0672 , C12N5/0678 , C12N5/068 , C12N5/0692 , C12N5/0693 , C12N5/0696 , C12N11/04 , C12N15/1034 , C12N2500/25 , C12N2500/90 , C12N2500/98 , C12N2500/99 , C12N2501/065 , C12N2501/105 , C12N2501/115 , C12N2501/119 , C12N2501/125 , C12N2501/13 , C12N2501/145 , C12N2501/155 , C12N2501/2306 , C12N2501/235 , C12N2501/237 , C12N2501/26 , C12N2501/998 , C12N2502/13 , C12N2502/99 , C12N2503/02 , C12N2506/02 , C12N2510/00 , C12N2510/04 , C12N2533/50 , C12N2533/90
摘要： This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
摘要翻译：本公开提供了一种用于培养人多能干细胞的改进系统。传统上，多能干细胞在一层饲养细胞（如小鼠胚胎成纤维细胞）上培养以防止它们分化。在这里描述的系统中，饲养细胞的作用由添加到培养环境中的组分代替，其支持快速增殖而不分化。有效的特征是细胞的合适的支持结构，以及可以在不被另一种细胞类型预处理的情况下可以新鲜添加到培养物中的有效培养基。在根据本发明的新鲜培养基中培养人胚胎干细胞导致细胞惊人地快速扩张，同时保持分化成代表所有三个胚胎胚层的细胞的能力。这种新的培养系统允许pPS细胞的大量增殖用于商业生产用于药物筛选和人类治疗的重要产品。

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