公开(公告)号：WO2014127219A1

公开(公告)日：2014-08-21

申请号：PCT/US2014/016448

申请日：2014-02-14

Applicant: THE CLEVELAND CLINIC FOUNDATION

Inventor： JENSEN, Jan ,  BUKYS, Mike ,  QU, Xiaoling ,  AFELIK, Solomon

IPC: C12N5/00

CPC classification number: C12N5/0676 ,  A61K9/1652 ,  A61K35/39 ,  C12N5/0678 ,  C12N2500/34 ,  C12N2500/38 ,  C12N2501/01 ,  C12N2501/11 ,  C12N2501/115 ,  C12N2501/119 ,  C12N2501/155 ,  C12N2501/21 ,  C12N2501/2306 ,  C12N2501/2311 ,  C12N2501/42 ,  C12N2501/998 ,  C12N2506/02 ,  C12N2506/1392

Abstract: A method of inducing pancreatic fates from human multipotent or pluripotent cells includes obtaining a cell population comprising human multipotent or pluripotent cells and providing the cell population with at least three of (i) an CXCR4 agonist, (ii) an EGFR agonist, (iii) an FGFR agonist, (iv) an Activin receptor agonist or an agent that stimulates SMAD3, (v) an IL11R agonist or IL6R agonist, (vi) a notch agonist, (vii) an RXR agonist or RAR agonist, or (viii) a BMP inhibitor for a time effective to allow the differentiation of pancreatic precursor cells from the human multipotent or pluripotent cells.

Abstract translation: 从人多能或多能细胞诱导胰腺命运的方法包括获得包含人多潜能细胞或多能细胞的细胞群，并向细胞群体提供至少三种（i）CXCR4激动剂，（ii）EGFR激动剂，（iii） 或（viii）一种FGFR激动剂，（iv）激活素受体激动剂或刺激SMAD3的药剂，（v）IL11R激动剂或IL6R激动剂，（vi）缺口激动剂，（vii）RXR激动剂或RAR激动剂，或 BMP抑制剂有效地允许胰腺前体细胞从人多能或多能细胞分化。

公开(公告)号：WO2020237141A1

公开(公告)日：2020-11-26

申请号：PCT/US2020/034201

申请日：2020-05-22

Applicant: THE CLEVELAND CLINIC FOUNDATION

Inventor： JENSEN, Jan ,  BUKYS, Michael A.

IPC: C07K14/475 ,  C07K14/51 ,  C12N5/00

Abstract: Provided herein are compositions, systems, kits, and methods for generating dorsal foregut endoderm (DFE) cells by contacting pluripotent stem cells with a retinoic acid signaling pathway agonist and a bone morphogenetic (BMP) pathway inhibitor without exposing the stem cells to a transforming growth factor beta (TGFβ) pathway agonist. In certain embodiments, the DFE cells are contacted with a retinoic acid signaling pathway agonist and a FGFR pathway inhibitor to generate pancreatic endoderm (PE) cells (e.g., with dorsal identity). In other embodiments, the PE cells are contacted with an ALK5 inhibitor and a Notch inhibitor to generate endocrine cells (e.g., insulin expressing endocrine cells). In certain embodiments, compositions, systems, kits, and methods are provided for generating anterior domain endoderm (ADE) cells.

公开(公告)号：WO2010054096A1

公开(公告)日：2010-05-14

申请号：PCT/US2009/063417

申请日：2009-11-05

Applicant: THE CLEVELAND CLINIC FOUNDATION ,  THE REGENT OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE ,  JENSEN, Jan ,  HUTTON, John ,  QU, Xiaoling ,  DAVIDSON, Howard

Inventor： JENSEN, Jan ,  HUTTON, John ,  QU, Xiaoling ,  DAVIDSON, Howard

IPC: C07K14/705 ,  C07K16/28 ,  G01N33/68

CPC classification number: G01N33/56966 ,  C07K14/705 ,  C07K14/70503 ,  C07K16/28 ,  C07K16/2803 ,  C07K2319/30 ,  C12N5/0676 ,  G01N33/5032 ,  G01N33/507 ,  G01N33/6893 ,  G01N2333/705 ,  G01N2800/042

Abstract: The invention is based, in part, on the discovery that a polypeptide, referred to herein as Betacam, is selectively expressed on the surface of pancreatic islet cells, Thus, in one aspect, the invention is directed to compositions comprising Betacam or that can be used to detect Betacam. In another aspect, the invention provides methods of detecting (e.g., non-invasively) pancreatic beta cells from a mammalian cell source. Another aspect of the invention is directed to cellular purification of pancreatic beta cells from a heterogeneous cell source of multiple kinds. In another aspect, the invention provides methods of identifying agents that modulate activity of Betacam- In yet another aspect, the invention provides for improved treatment and diagnosis of diabetes.

Abstract translation: 本发明部分地基于以下发现：本文称为Betacam的多肽在胰岛细胞的表面上选择性表达。因此，一方面，本发明涉及包含Betacam或可以是 用于检测Betacam。 另一方面，本发明提供了从哺乳动物细胞来源检测（例如非侵入性）胰腺β细胞的方法。 本发明的另一方面涉及从多种异质细胞来源的胰腺β细胞的细胞纯化。 另一方面，本发明提供了鉴定调节Betacam-In活性的试剂的方法。另一方面，本发明提供改进的糖尿病治疗和诊断。

公开(公告)号：WO2011011349A2

公开(公告)日：2011-01-27

申请号：PCT/US2010/042504

申请日：2010-07-20

Applicant: CENTOCOR ORTHO BIOTECH INC. ,  THE CLEVELAND CLINIC FOUNDATION ,  XU, Jean ,  JENSEN, Jan

Inventor： XU, Jean ,  JENSEN, Jan

IPC: C12N5/071 ,  C12N5/0735 ,  C12N5/02

CPC classification number: C12N5/0678 ,  C12N2501/115 ,  C12N2501/117 ,  C12N2501/15 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/385 ,  C12N2501/41 ,  C12N2501/415 ,  C12N2506/02 ,  C12N2533/90

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells into cells expressing markers characteristic of the pancreatic endocrine lineage that co-express PDX1, NKX6.1, but do not express CDX2 and NGN3.

Abstract translation: 本发明提供了促进多能干细胞分化为表达共表达PDX1，NKX6.1但不表达CDX2和NGN3的胰腺内分泌谱系特征性标志物的细胞的方法。 / p>