公开(公告)号：WO2008102000A1

公开(公告)日：2008-08-28

申请号：PCT/EP2008/052153

申请日：2008-02-21

Applicant: SARL ENDOCELLS ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  CZERNICHOW, Paul ,  SCHARFMANN, Raphaël ,  RAVASSARD, Philippe

Inventor： CZERNICHOW, Paul ,  SCHARFMANN, Raphaël ,  RAVASSARD, Philippe

IPC: C12N5/06 ,  G01N33/68

CPC classification number: C12N5/0676 ,  A61K35/12 ,  C12N5/0693 ,  C12N2500/90 ,  C12N2503/00 ,  C12N2503/02 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/52 ,  C12N2533/90 ,  G01N2800/042

Abstract: The present invention relates to a method for preparing commercial scale quantities of human functional Betacells and to the establishmentofcell lines. It also relates to a method of diagnosis using Beta cell tumorsor cells derived thereof. The method comprisessub-transplantation procedure to enrich the graft in proliferating Betacells, allowingtogenerate human Betacell lines. Such lines express little amount of insulin and have a gene expression profile that resembles to adult Betacells. In addition, the human Betacell lines are able to normalize glycemia of diabetic mice when transplanted,demonstrating their insulin secretion capabilities.

Abstract translation: 本发明涉及一种制备商业规模数量的人类功能性Betacells和建立细胞系的方法。 它还涉及使用β细胞瘤或其衍生的细胞进行诊断的方法。 该方法包括在增殖的Betacells中丰富移植物的移植手段，从而产生人Betacell细胞系。 这样的线表达少量的胰岛素，并且具有类似于成年Betacell的基因表达谱。 此外，人类Betacell系列能够在移植时使糖尿病小鼠的血糖正常化，从而证明其胰岛素分泌能力。

公开(公告)号：WO2008021577A2

公开(公告)日：2008-02-21

申请号：PCT/US2007/060987

申请日：2007-01-24

Applicant: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS ,  OBERHOLZER, José

Inventor： OBERHOLZER, José

IPC: A61K35/39 ,  A61K38/42

CPC classification number: C12N5/0676 ,  A01N1/02 ,  A01N1/0226 ,  A61K35/39 ,  A61K38/42 ,  A61K38/482 ,  A61K38/4886 ,  A61K2300/00

Abstract: Solutions and suspensions comprising polymerized hemoglobin derived from human blood are disclosed. The solutions and suspensions may comprise cell culture medium, an enzyme (such as a protease), and/or a buffer. Processes of preparing the solutions and suspensions are also disclosed. The solutions and suspensions may be employed in methods of isolating mammalian cells, such as pancreatic islets, methods of preserving mammalian tissue and organs, methods of aiding the recovery of mammalian cells following their isolation, methods of maintaining mammalian cells, methods of propagating mammalian cells, and methods of treating a mammal with diabetes.

Abstract translation: 公开了包含源自人血液的聚合血红蛋白的溶液和混悬液。 溶液和悬浮液可以包含细胞培养基，酶（例如蛋白酶）和/或缓冲液。 还公开了制备溶液和悬浮液的方法。 溶液和悬浮液可用于分离哺乳动物细胞如胰岛的方法，保存哺乳动物组织和器官的方法，帮助哺乳动物细胞分离后回收哺乳动物细胞的方法，维持哺乳动物细胞的方法，繁殖哺乳动物细胞的方法 以及治疗患有糖尿病的哺乳动物的方法。

公开(公告)号：WO2008013664A2

公开(公告)日：2008-01-31

申请号：PCT/US2007/015536

申请日：2007-07-05

Applicant: CYTHERA, INC. ,  MARTINSON, Laura ,  KROON, Evert ,  D'AMOUR, Kevin ,  BAETGE, Emmanuel Edward

Inventor： MARTINSON, Laura ,  KROON, Evert ,  D'AMOUR, Kevin ,  BAETGE, Emmanuel Edward

IPC: C12N5/06

CPC classification number: C12N5/0676 ,  C12N5/0678 ,  C12N2500/38 ,  C12N2501/10 ,  C12N2501/105 ,  C12N2501/115 ,  C12N2501/12 ,  C12N2501/16 ,  C12N2501/33 ,  C12N2501/385 ,  C12N2501/41 ,  C12N2501/415 ,  C12N2501/42 ,  C12N2501/58 ,  C12N2501/999 ,  C12N2506/02

Abstract: Disclosed herein are methods of producing pancreatic hormone-expressing cells by first differentiating pluripotent cells in cell culture so as to produce endodermal cells, the endodermal cells being competent to further differentiate into hormone-expressing cells capable of secreting at least one pancreatic hormone in response to a physiological signal, and then, transplanting the cultured endodermal cells into an organism, such as an organism in need of an endocrine cell therapy.

Abstract translation: 本文公开了通过在细胞培养物中首先分化多能细胞以产生内胚层细胞来产生表达胰腺激素的细胞的方法，所述内胚层细胞能够进一步分化成能够分泌至少一种胰激素的激素表达细胞，以响应于 生理信号，然后将培养的内胚层细胞移植到生物体如需要内分泌细胞治疗的生物体中。

公开(公告)号：WO2007143193A1

公开(公告)日：2007-12-13

申请号：PCT/US2007/013137

申请日：2007-06-04

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  DALTON, Stephen ,  REYNOLDS, David ,  KULIK, Michael

Inventor： DALTON, Stephen ,  REYNOLDS, David ,  KULIK, Michael

IPC: C12N5/08

CPC classification number: C12N5/067 ,  C12N5/0676 ,  C12N2501/115 ,  C12N2501/119 ,  C12N2501/16 ,  C12N2501/385 ,  C12N2501/415 ,  C12N2501/70 ,  C12N2502/13 ,  C12N2506/02

Abstract: The invention relates to methods that allow for the efficient differentiation to form pancreatic endoderm cells from pluripotent stem cells such as human embryonic stem cells and definitive endoderm cells. The invention is directly applicable to the ultimate generation of pancreatic beta cells that could be used as part of a therapy to treat or even cure diabetes. Additionally, the present invention may be used to generate liver endoderm cells from human embryonic stem cells and definite endoderm cells as well. This invention relates to a method for generating definitive endoderm and pancreatic endoderm cells from stem cells, preferably human embryonic stem cells using defined media in the absence of feeder cells. A simply two step procedure to provide pancreatic endoderm cells from embryonic stem cells represents further embodiments of the present invention.

Abstract translation: 本发明涉及允许有效分化以从多能干细胞如人胚胎干细胞和确定性内胚层细胞形成胰腺内胚层细胞的方法。 本发明可直接应用于可用作治疗或甚至治愈糖尿病的治疗的一部分的胰腺β细胞的最终产生。 此外，本发明也可用于从人胚胎干细胞和确定的内胚层细胞产生肝内胚层细胞。 本发明涉及一种用于在不存在饲养细胞的情况下使用限定的培养基从干细胞产生确定性内胚层和胰腺内胚层细胞的方法，优选人胚胎干细胞。 从胚胎干细胞提供胰腺内胚层细胞的简单的两步法代表了本发明的另外的实施方案。

公开(公告)号：WO2007135563A2

公开(公告)日：2007-11-29

申请号：PCT/IB2007/002165

申请日：2007-04-16

Applicant: CONSORTIUM NATIONAL DE RECHERCHE EN GENOMIQUE (CNRG) ,  JULIER, Cécile ,  TAHA, Doris ,  NICOLINO, Marc ,  CAVENER, Douglas

Inventor： JULIER, Cécile ,  TAHA, Doris ,  NICOLINO, Marc ,  CAVENER, Douglas

IPC: C12N5/071

CPC classification number: C12Q1/6883 ,  A61K38/1709 ,  C12N5/0676 ,  C12N2501/60 ,  C12N2501/998 ,  C12N2506/02 ,  C12N2506/03 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2600/172

Abstract: The present invention relates to a method of diagnosis of neonatal diabetes, congenital hypothyroidism and congenital glaucoma, comprising detecting the presence of a mutation in the GLIS3 gene and to a method for preparing functional pancreatic beta-cells by culturing human multipotent or pluripotent cells, such as embryonic stem cells (ES-cells) or human somatic stem cells in a culture medium comprising a effective amount of GLIS3 to induce said cells differenciation into functional pancreatic beta-cells producing insulin. It also relates to a pharmaceutical composition comprising GLIS3 as active ingredient.

Abstract translation: 本发明涉及新生儿糖尿病，先天性甲状腺功能减退症和先天性青光眼的诊断方法，包括检测GLIS3基因中突变的存在以及通过培养人多能或多能细胞来制备功能性胰腺β-细胞的方法，例如 作为包含有效量的GLIS3以诱导所述细胞的培养基中的胚胎干细胞（ES-细胞）或人体细胞干细胞分化成产生胰岛素的功能胰腺β-细胞。 它还涉及包含GLIS3作为活性成分的药物组合物。

公开(公告)号：WO2007131209A2

公开(公告)日：2007-11-15

申请号：PCT/US2007/068303

申请日：2007-05-04

Applicant: OPEXA THERAPEUTICS ,  WINNIER, Glenn, E. ,  NEWSOM, Brian, S. ,  RILL, Donna, R. ,  WILLIAMS, Jim, C.

Inventor： WINNIER, Glenn, E. ,  NEWSOM, Brian, S. ,  RILL, Donna, R. ,  WILLIAMS, Jim, C.

IPC: C12N5/08

CPC classification number: C12N5/0676 ,  C12N2500/25 ,  C12N2500/34 ,  C12N2500/38 ,  C12N2501/052 ,  C12N2501/105 ,  C12N2501/11 ,  C12N2501/12 ,  C12N2501/22 ,  C12N2501/235 ,  C12N2501/52 ,  C12N2506/11

Abstract: The generation of pancreatic islet-like cells from isolated monocyte-derived stem cells (MDSCs) is provided. MDSCs may be differentiated into pancreatic islet cells by contacting the MDSCs with a differentiation factor or factors. Compositions comprising pancreatic islet cells and methods of using them are also provided.

Abstract translation: 提供了来自分离的单核细胞来源的干细胞（MDSC）的胰岛样细胞的产生。 MDSC可以通过使MDSC与分化因子或因子接触来分化成胰岛细胞。 还提供了包含胰岛细胞的组合物及其使用方法。

公开(公告)号：WO02074946A8

公开(公告)日：2007-11-01

申请号：PCT/DK0200130

申请日：2002-02-26

Applicant: NOVO NORDISK AS

Inventor： SERUP PALLE ,  HEIMBERG HARRY ,  GRADWOHL GERARD

IPC: A61K35/12 ,  C12N5/071

CPC classification number: C12N5/0676 ,  A61K35/12 ,  C12N2501/60 ,  C12N2502/02 ,  C12N2503/02 ,  C12N2510/02

Abstract: The invention relates to methods for generating insulin secreting cells from precursor stem cells or from adult pancreatic exocrine cells by exposing them to a nucleic acid molecule encoding neurogenin3 (ngn3) or NeuroD/ ß2. The methods of the invention are useful, for example, for generation of glucose sensitive insulin-secreting ß-cells suitable for transplantation, as well as for in situ development of insulin-secreting cells in a patient in need thereof. Further, the method of the invention relates to methods for preventing premature differentiation of precursor stem cells into insulin-secreting ß-cells. Still further, the invention relates to assay methods for identification of compounds that prevent or activate ß-cell differentiation.

Abstract translation: 本发明涉及通过将其暴露于编码neurogenin3（ngn3）或NeuroD /β2的核酸分子从前体干细胞或成年胰腺外分泌细胞产生胰岛素分泌细胞的方法。 本发明的方法可用于例如适用于移植的葡萄糖敏感型胰岛素分泌型β细胞的产生，以及用于有需要的患者中胰岛素分泌细胞的原位发育。 此外，本发明的方法涉及用于预防前体干细胞过早分化成胰岛素分泌型β细胞的方法。 此外，本发明涉及用于鉴定预防或激活β细胞分化的化合物的测定方法。

公开(公告)号：WO2007037407A1

公开(公告)日：2007-04-05

申请号：PCT/JP2006/319528

申请日：2006-09-29

Applicant: 国立大学法人岡山大学 ,  株式会社スリー・ディー・マトリックス・ジャパン ,  小林 直哉 ,  田中 紀章

Inventor： 小林 直哉 ,  田中 紀章

IPC: C12N5/06 ,  A61L27/00

CPC classification number: C12N5/0671 ,  C12N5/067 ,  C12N5/0676 ,  C12N2533/50 ,  C12N2533/52 ,  C12N2533/54

Abstract: 　細胞の培養方法に関し、ブタ肝細胞、ヒト肝細胞、ブタ膵島、ヒト膵島などの細胞を、細胞の生存、細胞形態および細胞機能が維持された状態で長期にわたって高次元培養するために、細胞をペプチドハイドロゲルを支持体として培養することを特徴とする細胞の培養方法を提供する。また、前記培養方法により得られる細胞およびペプチドハイドロゲルを含む細胞培養物、該細胞培養物を含むバイオリアクターならびに細胞培養物を含む細胞製剤を提供する。

Abstract translation: 公开了一种在细胞的存活，形态和功能的状态下长时间进行细胞（例如猪或人肝细胞，猪或人胰岛细胞）的高维培养的细胞培养方法 被维护。 该方法的特征在于使用肽水凝胶作为载体来培养细胞。 还公开了通过培养方法产生的细胞，含有肽水凝胶的细胞培养物，包含细胞培养物的生物反应器和包含细胞培养物的细胞制备物。

公开(公告)号：WO2006016999A1

公开(公告)日：2006-02-16

申请号：PCT/US2005/022604

申请日：2005-06-23

Applicant: NOVOCELL, INC. ,  D'AMOUR, Kevin, Allen ,  AGULNICK, Alan, D. ,  ELIAZER, Susan ,  BAETGE, Emmanuel

Inventor： D'AMOUR, Kevin, Allen ,  AGULNICK, Alan, D. ,  ELIAZER, Susan ,  BAETGE, Emmanuel

IPC: C12N5/06

CPC classification number: C12N5/0018 ,  A61K35/12 ,  C12N5/0603 ,  C12N5/0606 ,  C12N5/0676 ,  C12N5/0679 ,  C12N15/1086 ,  C12N2500/90 ,  C12N2501/115 ,  C12N2501/119 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/385 ,  C12N2501/415 ,  C12N2502/02 ,  C12N2502/13 ,  C12N2503/00 ,  C12N2506/02 ,  C12N2510/00 ,  C12Q1/6881 ,  C12Q2600/158

Abstract: Disclosed herein are methods of identifying one or more differentiation factors that are useful for differentiating cells in a cell population comprising definitive endoderm cells into cells which are capable of forming tissues and/or organs that are derived from the gut tube.

Abstract translation: 本文公开了鉴定一种或多种分化因子的方法，所述分化因子可用于将包含定形内胚层细胞的细胞群中的细胞分化成能够形成源自肠管的组织和/或器官的细胞。

公开(公告)号：WO2006007377A2

公开(公告)日：2006-01-19

申请号：PCT/US2005/021186

申请日：2005-06-16

Applicant: THE GENERAL HOSPITAL CORPORATION ,  HABENER, Joel F. ,  THOMAS, Melissa K. ,  GRAGNOLI, Claudia

Inventor： HABENER, Joel F. ,  THOMAS, Melissa K. ,  GRAGNOLI, Claudia

IPC: C12Q1/68

CPC classification number: A61K38/22 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0325 ,  A01K2267/0362 ,  A61K31/165 ,  A61K31/573 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4702 ,  C12N5/0676 ,  C12N15/8509 ,  C12N2501/16 ,  C12N2501/33

Abstract: The present invention is directed to the use of Bridge-1 polynucleotides and Bridge-1 polypeptides, as well as activators and inhibitors of Bridge-1 activity, in the diagnosis and treatment of Bridge-1 mediated disorders, including diabetes.

Abstract translation: 本发明涉及Bridge-1多核苷酸和Bridge-1多肽以及Bridge-1活性的激活剂和抑制剂在桥-1介导的病症包括糖尿病的诊断和治疗中的用途。