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1. 发明授权

US08951800B2 Primate pluripotent stem cell expansion without feeder cells and in the presence of FGF and matrigel or Engelbreth-Holm-Swarm tumor cell preparation 有权
标题翻译：灵长类多能干细胞扩增无饲养细胞，并存在FGF和基质胶或恩格布氏 - 霍姆群肿瘤细胞制备
公开(公告)号：US08951800B2
公开(公告)日：2015-02-10
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： C12N5/02 , C12N15/10 , C12N5/0735 , C12N5/0793 , C12N5/079 , 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.
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。

2. 发明授权

US07732199B2 Process for making transplantable cardiomyocytes from human embryonic stem cells 有权
标题翻译：从人胚胎干细胞制备可移植的心肌细胞的方法
公开(公告)号：US07732199B2
公开(公告)日：2010-06-08
申请号：US10805099
申请日：2004-03-19
申请人： Chunhui Xu , Joseph D. Gold
发明人： Chunhui Xu , Joseph D. Gold
IPC分类号： C12N5/08
CPC分类号： C12N5/0606 , A61K35/12 , C12N5/0657 , C12N2500/30 , C12N2500/44 , C12N2500/62 , C12N2501/06 , C12N2501/105 , C12N2501/15 , C12N2501/155 , C12N2501/16 , C12N2501/385 , C12N2501/999 , C12N2503/02 , C12N2506/02 , C12N2510/00
摘要： This invention provides populations human cells of the cardiomyocyte lineage. The cells are obtained by causing cultures of pluripotent stem cells to differentiate in vitro, and then harvesting cells with certain phenotypic features. Differentiated cells bear cell surface and morphologic markers characteristic of cardiomyocytes, and a proportion of them undergo spontaneous periodic contraction. Highly enriched populations of cardiomyocytes and their replicating precursors can be obtained, suitable for use in a variety of applications, such as drug screening and therapy for cardiac disease.
摘要翻译：本发明提供了心肌细胞谱系的群体人细胞。通过使多能干细胞的培养物在体外分化获得细胞，然后收获具有某些表型特征的细胞。分化细胞具有心肌细胞特征的细胞表面和形态学标记，其中一部分经历自发性周期性收缩。可以获得高度富集的心肌细胞群及其复制前体，适用于各种应用，如药物筛选和心脏病治疗。

3. 发明申请

US20080299582A1 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：US20080299582A1
公开(公告)日：2008-12-04
申请号：US12170219
申请日：2008-07-09
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 , C12N15/87 , C12N5/06 , 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。

4. 发明授权

US07041438B2 Use of human embryonic stem cells for drug screening and toxicity testing 有权
标题翻译：使用人类胚胎干细胞进行药物筛选和毒性测试
公开(公告)号：US07041438B2
公开(公告)日：2006-05-09
申请号：US10039956
申请日：2001-10-23
申请人： Melissa K. Carpenter , Margaret S. Inokuma , Chunhui Xu
发明人： Melissa K. Carpenter , Margaret S. Inokuma , Chunhui Xu
IPC分类号： C12Q3/00 , C12Q1/02 , C12N5/00 , C12N5/02 , C12N5/06 , C12N5/08
CPC分类号： C12N5/0606 , A61K35/12 , C12N15/1034 , C12N15/1072 , C12N15/1096 , C12N2500/14 , C12N2500/30 , C12N2500/38 , C12N2500/44 , C12N2500/62 , C12N2501/105 , C12N2501/13 , C12N2501/155 , C12N2501/385 , C12N2501/39 , C12N2501/999 , C12N2502/13 , C12N2502/99 , C12N2503/02 , C12N2510/00 , C12N2510/04 , C12N2533/90
摘要： This disclosure provides an improved system for culturing human pluripotent stem (pPS) cells in the absence of feeder cells. The role of the feeder cells can be replaced by supporting the culture on an extracellular matrix, and culturing the cells in a conditioned medium. Permanent cell lines are provided that can produce conditioned medium on a commercial scale. Methods have also been discovered to genetically alter pPS cells by introducing the cells with a viral vector or DNA/lipid complex. The system described in this disclosure allows for bulk proliferation of pPS cells for use in studying the biology of pPS cell differentiation, and the production of important products for use in human therapy.
摘要翻译：本公开提供了在不存在饲养细胞的情况下培养人多能干（pPS）细胞的改进系统。饲养细胞的作用可以通过将培养物支持在细胞外基质上并在条件培养基中培养细胞来代替。提供可以商业规模生产条件培养基的永久性细胞系。还已经发现通过用病毒载体或DNA /脂质复合体引入细胞来遗传地改变pPS细胞的方法。本公开中描述的系统允许pPS细胞的体积增殖用于研究pPS细胞分化的生物学和用于人类治疗的重要产物的生产。

5. 发明申请

US20050054092A1 Process for making transplantable cardiomyocytes from human embryonic stem cells 有权
标题翻译：从人胚胎干细胞制备可移植的心肌细胞的方法
公开(公告)号：US20050054092A1
公开(公告)日：2005-03-10
申请号：US10805099
申请日：2004-03-19
申请人： Chunhui Xu , Joseph Gold
发明人： Chunhui Xu , Joseph Gold
IPC分类号： A61K35/12 , C12N5/0735 , C12N5/077 , C12N5/08
CPC分类号： C12N5/0606 , A61K35/12 , C12N5/0657 , C12N2500/30 , C12N2500/44 , C12N2500/62 , C12N2501/06 , C12N2501/105 , C12N2501/15 , C12N2501/155 , C12N2501/16 , C12N2501/385 , C12N2501/999 , C12N2503/02 , C12N2506/02 , C12N2510/00
摘要： This invention provides populations human cells of the cardiomyocyte lineage. The cells are obtained by causing cultures of pluripotent stem cells to differentiate in vitro, and then harvesting cells with certain phenotypic features. Differentiated cells bear cell surface and morphologic markers characteristic of cardiomyocytes, and a proportion of them undergo spontaneous periodic contraction. Highly enriched populations of cardiomyocytes and their replicating precursors can be obtained, suitable for use in a variety of applications, such as drug screening and therapy for cardiac disease.
摘要翻译：本发明提供了心肌细胞谱系的群体人细胞。通过使多能干细胞的培养物在体外分化获得细胞，然后收获具有某些表型特征的细胞。分化细胞具有心肌细胞特征的细胞表面和形态学标记，其中一部分经历自发性周期性收缩。可以获得高度富集的心肌细胞群及其复制前体，适用于各种应用，如药物筛选和心脏病治疗。

6. 发明授权

US06642048B2 Conditioned media for propagating human pluripotent stem cells 有权
公开(公告)号：US06642048B2
公开(公告)日：2003-11-04
申请号：US09900752
申请日：2001-07-06
申请人： Chunhui Xu , Joseph D. Gold
发明人： Chunhui Xu , Joseph D. Gold
IPC分类号： C12N508
CPC分类号： C12N5/0606 , A61K35/12 , C12N15/1034 , C12N15/1072 , C12N15/1096 , C12N2500/14 , C12N2500/30 , C12N2500/38 , C12N2500/44 , C12N2500/62 , C12N2501/105 , C12N2501/13 , C12N2501/155 , C12N2501/385 , C12N2501/39 , C12N2501/999 , C12N2502/13 , C12N2502/99 , C12N2503/02 , C12N2510/00 , C12N2510/04 , C12N2533/90
摘要： This invention provides media that support the growth of primate pluripotent stem cells in feeder-free culture, and cell lines useful for producing such media and other purposes. Conventionally, it has been necessary to grow pluripotent embryonic cells on feeder layers of primary embryonic fibroblasts, in order to prevent them from differentiating. It has now been discovered that standard culture media conditioned by special cell lines can be used to support proliferation of pluripotent stem cells while inhibiting differentiation in an environment free of feeder cells. This invention includes mesenchymal and fibroblast-like cell lines obtained from embryonic tissue or differentiated from embryonic stem cells. Methods for deriving such cell lines, processing media, and growing stem cells using the conditioned media are described and illustrated in this disclosure.

7. 发明授权

US06226112B1 Optical time-division-multiplex system 失效
标题翻译：光时分复用系统
公开(公告)号：US06226112B1
公开(公告)日：2001-05-01
申请号：US09099788
申请日：1998-06-18
申请人： Winfried Denk , Gadi Lenz , Joseph Shmulovich , Chunhui Xu
发明人： Winfried Denk , Gadi Lenz , Joseph Shmulovich , Chunhui Xu
IPC分类号： H04J1408
CPC分类号： H04J14/08
摘要： In a time-division-multiplex system, a relatively high-rate optical signal stream comprising multiple interleaved signal sequences is applied to one end of an elongated waveguide that includes multiple photodetectors disposed along the longitudinal extent of the waveguide. Probe pulses at a relatively low rate are applied to the other end of the waveguide in a synchronized fashion to cause two-photon non-linear absorption in successive respective photodetectors as each propagating probe pulse overlaps successive different signals of each sequence. In that way, electrical output signals are provided from each photodetector at the relatively low probe-pulse rate.
摘要翻译：在时分多路复用系统中，将包括多个交错信号序列的相对高速率的光信号流施加到细长波导的一端，该波导包括沿波导的纵向延伸设置的多个光电探测器。以相对低的速率的探针脉冲以同步方式施加到波导的另一端，以在连续的各个光电检测器中引起双光子非线性吸收，因为每个传播的探针脉冲与每个序列的连续的不同信号重叠。以这种方式，以相对低的探针脉冲速率从每个光电检测器提供电输出信号。

8. 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。

9. 发明授权

US08097458B2 Micro-carrier culture system for rapid expansion of human embryonic stem cells 有权
标题翻译：用于人类胚胎干细胞快速扩增的微载体培养系统
公开(公告)号：US08097458B2
公开(公告)日：2012-01-17
申请号：US12763884
申请日：2010-04-20
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： C12N15/02
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）上培养以防止其分化。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。

10. 发明申请

US20090047739A1 Direct Differentiation Method for Making Cardiomyocytes from Human Embryonic Stem Cells 有权
标题翻译：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：US20090047739A1
公开(公告)日：2009-02-19
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： C12N5/06
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。

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