公开(公告)号：EP1317289A2

公开(公告)日：2003-06-11

申请号：EP01971139.9

申请日：2001-09-11

Applicant: The Regents of the University of California ,  Chien, Kenneth R. ,  Hoshijima, Masahiko ,  Ross, John, Jr. ,  Ikeda, Yasuhiro

Inventor： CHIEN, Kenneth, R. ,  HOSHIJIMA, Masahiko ,  ROSS, John, Jr. ,  IKEDA, Yasuhiro,Yamaguchi Univ. Sch. of Med.

IPC: A61K48/00

CPC classification number: A61K38/1709 ,  A61K31/4045 ,  A61K31/417 ,  A61K38/046 ,  A61K38/177 ,  A61K38/1787 ,  A61K38/46 ,  A61K45/06 ,  A61K48/00 ,  A61K48/0008 ,  A61K48/0083 ,  C12N2710/10043 ,  C12N2750/14143 ,  A61K2300/00

Abstract: Methods for the delivery of genes to improve cardiac function including the use of viral vectors, isolation of the heart from systemic circulation, and induction of hypothermia/cardiac arrest are described. The method results in high-level, long-term expression of reporter genes and enhanced cardiac function in hamster models of heart disease.

公开(公告)号：IL314150A

公开(公告)日：2024-09-01

申请号：IL31415024

申请日：2024-07-07

Applicant: SMARTCELLA SOLUTIONS AB ,  YANG RAN ,  CHIEN KENNETH R

Inventor： YANG RAN ,  CHIEN KENNETH R

Abstract: Methods for generating human induced mesenchymal stem cells (iMSC) from human pluripotent stem cells, such as embryonic stem cells, are provided. Progenitors of iMSCs are first generated in a two-step protocol, with further differentiation to iMSCs accomplished by a third step culture. The iMSCs express mesenchymal surface markers and exhibit trilineage differentiation to adipocytes, osteocytes and chondrocytes. Culture media, methods of isolating extracellular vesicles from the iMSCs and kits are also provided.

公开(公告)号：AU9106301A

公开(公告)日：2002-03-26

申请号：AU9106301

申请日：2001-09-11

Applicant: UNIV CALIFORNIA ,  CHIEN KENNETH R ,  HOSHIJIMA MASAHIKO ,  ROSS JOHN ,  IKEDA YASUHIRO

Inventor： CHIEN KENNETH R ,  HOSHIJIMA MASAHIKO ,  ROSS JOHN ,  IKEDA YASUHIRO

IPC: A61K38/17 ,  A61K38/46 ,  A61K48/00 ,  A61P9/00 ,  C12N15/12

Abstract: Methods for the delivery of genes to improve cardiac function including the use of viral vectors, isolation of the heart from systemic circulation, and induction of hypothermia/cardiac arrest are described. The method results in high-level, long-term expression of reporter genes and enhanced cardiac function in hamster models of heart disease.

公开(公告)号：WO2008054819A2

公开(公告)日：2008-05-08

申请号：PCT/US2007/023155

申请日：2007-11-02

Applicant: THE GENERAL HOSPITAL CORPORATION ,  CHIEN, Kenneth, R. ,  CARON, Leslie ,  NAKANO, Atsushi ,  MORETTI, Allesandra

Inventor： CHIEN, Kenneth, R. ,  CARON, Leslie ,  NAKANO, Atsushi ,  MORETTI, Allesandra

IPC: C12N5/00

CPC classification number: C12N5/0662 ,  C12N5/0657 ,  C12N2502/1329 ,  C12N2506/02

Abstract: The present invention relates to isolation of cardiovascular stem cells, and more particularly to cardiovascular stem cells positive for markers isll + /Nkx2.5 + /flkl + and cardiovascular stem cells which can differentiate along endothelial, cardiac, and smooth muscle cell lineages. The invention relates to uses of the cardiovascular stem cells, in particular for the treatment of cardiovascular disorders and as an assay comprising a plurality of cardiovascular stem cells. The invention also relates to a method for isolation and enrichment of stem cells using mesenchymal cell feeder layer and uses of mesenchymal feeder layer as a screening assay for agents which effect stem cells.

Abstract translation: 本发明涉及心血管干细胞的分离，更具体地说，涉及用于标记的阳性的心血管干细胞。

公开(公告)号：WO2008054819A3

公开(公告)日：2009-03-26

申请号：PCT/US2007023155

申请日：2007-11-02

Applicant: GEN HOSPITAL CORP ,  CHIEN KENNETH R ,  CARON LESLIE ,  NAKANO ATSUSHI ,  MORETTI ALLESANDRA

Inventor： CHIEN KENNETH R ,  CARON LESLIE ,  NAKANO ATSUSHI ,  MORETTI ALLESANDRA

IPC: C12N5/00

CPC classification number: C12N5/0662 ,  C12N5/0657 ,  C12N2502/1329 ,  C12N2506/02

Abstract: The present invention relates to isolation of cardiovascular stem cells, and more particularly to cardiovascular stem cells positive for markers isll + /Nkx2.5 + /flkl + and cardiovascular stem cells which can differentiate along endothelial, cardiac, and smooth muscle cell lineages. The invention relates to uses of the cardiovascular stem cells, in particular for the treatment of cardiovascular disorders and as an assay comprising a plurality of cardiovascular stem cells. The invention also relates to a method for isolation and enrichment of stem cells using mesenchymal cell feeder layer and uses of mesenchymal feeder layer as a screening assay for agents which effect stem cells.

Abstract translation: 本发明涉及心血管干细胞的分离，更具体地涉及可以沿内皮，心脏和平滑肌细胞谱系分化的标记物isll + / Nkx2.5 + / flk1 +和心血管干细胞阳性的心血管干细胞。 本发明涉及心血管干细胞的用途，特别是用于治疗心血管疾病以及作为包含多个心血管干细胞的测定法。 本发明还涉及使用间充质细胞饲养层分离和富集干细胞的方法，并且使用间充质饲养层作为影响干细胞的药剂的筛选试验。

公开(公告)号：WO2017172086A1

公开(公告)日：2017-10-05

申请号：PCT/US2017/017952

申请日：2017-02-15

Applicant: LEUNG, Chuen, Yan ,  CLARKE, Jonathan ,  XU, Jiejia ,  SANTORO, Federica ,  SAHARA, Makoto ,  CHIEN, Kenneth, R.

Inventor： LEUNG, Chuen, Yan ,  CLARKE, Jonathan ,  XU, Jiejia ,  SANTORO, Federica ,  SAHARA, Makoto ,  CHIEN, Kenneth, R.

IPC: C12Q1/68 ,  C12N5/077 ,  G01N33/50

Abstract: The present invention provides genetic markers for identifying engraftable human cardiac ventricular progenitor cells. The engraftment markers of the invention include angiogenic markers and extracellular matrix markers. Human ventricular progenitor cells expressing these markers are capable of forming ventricular tissue in vivo that is vascularized and supported by an extracellular matrix. Methods of engrafting human cardiac ventricular progenitor cells by transplanting into a subject progenitor cells that express the engraftment markers are also provided.

Abstract translation: 本发明提供了用于鉴定可雕刻的人心脏心室祖细胞的遗传标记。 本发明的植入标记包括血管生成标记和细胞外基质标记。 表达这些标记物的人类心室祖细胞能够在体内形成心室组织，其被血管化并由细胞外基质支持。 还提供了通过移植到表达植入标记的受试者祖细胞中来植入人心脏心室祖细胞的方法。

公开(公告)号：WO2016029122A1

公开(公告)日：2016-02-25

申请号：PCT/US2015/046309

申请日：2015-08-21

Applicant: CHIEN, Kenneth, R. ,  LIAN, Xiaojun

Inventor： CHIEN, Kenneth, R. ,  LIAN, Xiaojun

IPC: C12N5/077

CPC classification number: C12N5/0657 ,  A61K35/34 ,  C12N2501/415 ,  C12N2501/42 ,  C12N2503/02 ,  C12N2506/02 ,  C12N2506/03 ,  C12N2506/45 ,  C12N2513/00

Abstract: The present invention provides Jagged 1 and Frizzled 4 as cell surface markers for isolating human cardiomyogenic ventricular progenitor cells, in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Thus, the invention provides human ventricular progenitor (HVP) cells. The invention provides in vitro methods of the separation of Islet 1+ Jagged 1+ ventricular progenitor cells and/or Islet 1+/Frizzled 4+ ventricular progenitor cells and/or Islet 1+/Jagged 1+/Frizzled 4+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells are also provided. Methods of in vivo use of Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.

Abstract translation: 本发明提供了Jagged1和Frizzled4作为细胞表面标志物，用于分离人心肌起始心室祖细胞，特别是优先分化成心室肌细胞的祖细胞。 因此，本发明提供了人心室祖细胞（HVP）细胞。 本发明提供分离Islet 1+ Jagged 1+心室祖细胞和/或胰岛1 + /卷曲4+心室祖细胞和/或胰岛1 + / Jagged 1 + /卷曲4+心室祖细胞的体外方法， 并大规模扩张和传播。 还提供了孤立的Jagged 1+和/或卷曲4+心室祖细胞的大克隆群体。 还提供了体内使用锯齿状1+和/或卷曲4+心室祖细胞用于心脏修复或改善心脏功能的方法。 还提供了使用锯齿状1+和/或卷曲4+心室祖细胞进行心脏毒性筛选测试化合物的方法。

公开(公告)号：WO2021003300A1

公开(公告)日：2021-01-07

申请号：PCT/US2020/040553

申请日：2020-07-01

Applicant: CHIEN, Kenneth R. ,  WITMAN, Nevin ,  FU, Wei

Inventor： CHIEN, Kenneth R. ,  WITMAN, Nevin ,  FU, Wei

IPC: C07K14/475 ,  A61K35/28 ,  C07K14/51 ,  C12N5/0775 ,  C12N15/11

Abstract: This disclosure relates to compositions including mesenchymal stem or stromal cells (MSCs) that harbor one or more modified RNA molecules encoding a bone morphogenetic protein (BMP), e.g., human BMP, and one or more modified RNA molecules encoding vascular endothelial growth factor (VEGF), e.g., human VEGF or VEGF-A, or first and second separate pluralities of MSCs, wherein each MSC in the first plurality of MSCs harbors one or more modified RNA molecules encoding BMP, and wherein each MSC in the second plurality of MSCs harbors one or more modified RNA molecules encoding VEGF; and a carrier, e.g., a solid or semi-solid carrier. The disclosure also relates to methods and uses of these compositions to treat bone defects.

公开(公告)号：WO2010042856A3

公开(公告)日：2010-07-22

申请号：PCT/US2009060224

申请日：2009-10-09

Applicant: GEN HOSPITAL CORP ,  HARVARD COLLEGE ,  CHIEN KENNETH R ,  DOMIAN IBRAHIM J ,  CHIRAVURI MURALI ,  VAN DER MEER PETER ,  PARKER KEVIN KIT ,  FEINBERG ADAM W

Inventor： CHIEN KENNETH R ,  DOMIAN IBRAHIM J ,  CHIRAVURI MURALI ,  VAN DER MEER PETER ,  PARKER KEVIN KIT ,  FEINBERG ADAM W

IPC: A61L27/38 ,  A61F2/08 ,  A61L27/14 ,  A61L27/24 ,  A61L27/54

CPC classification number: A61L27/3804 ,  A61L27/507 ,  A61L27/54 ,  A61L2300/252 ,  A61L2300/258 ,  A61L2300/414 ,  A61L2300/426 ,  A61L2300/43 ,  A61L2300/432

Abstract: The present invention generally relates to a population of committed ventricular progenitor (CVP) cells and their use to generate a tissue engineered myocardium, in particular two dimensional tissue engineered myocardium which is comparable to functional ventricular heart muscle. One embodiment of present invention provides a composition and methods for the production of a tissue engineered myocardium which has functional properties of cardiac muscle, such as contractibility (e.g. contraction force) and numerous properties of mature fully functional ventricular heart muscle tissue. In particular, in one embodiment, a composition comprising the tissue engineered myocardium comprises committed ventricular progenitor (CVP) cells seeded on a free-standing biopolymer structure to form functional ventricular myocardium tissue.

Abstract translation: 本发明一般涉及定向心室祖细胞（CVP）细胞群及其用于产生组织工程化心肌的用途，特别是与功能性心室肌相当的二维组织工程心肌。 本发明的一个实施方案提供了用于生产具有心肌功能特性（例如收缩力（例如收缩力））和成熟全功能心室肌组织的众多特性的组织工程心肌的组合物和方法。 特别地，在一个实施方案中，包含组织工程化心肌的组合物包含种植于自立式生物聚合物结构上的定向心室祖细胞（CVP）细胞以形成功能性心室心肌组织。

公开(公告)号：WO2008098184A2

公开(公告)日：2008-08-14

申请号：PCT/US2008/053449

申请日：2008-02-08

Applicant: THE GENERAL HOSPITAL CORPORATION ,  CHIEN, Kenneth R. ,  QYANG, Yibing ,  MARTIN-PUIG, Silvia

Inventor： CHIEN, Kenneth R. ,  QYANG, Yibing ,  MARTIN-PUIG, Silvia

IPC: C12N5/00

CPC classification number: C12N5/0668 ,  C12N2501/415 ,  C12N2502/02 ,  C12N2502/1329

Abstract: The present invention relates to methods for the induction and a cell to enter the Islet 1 + (Isl1 + ) lineage and methods for expansion of cells of islet 1 + lineage. One aspect of the present invention relates to methods to induce a cell to enter the islet 1 + lineage, and more particularly to a method to induce a cell to enter a the Isl1 + lineage to become an Isl1 + progenitor that is capable of differentiating along multiple different lineages such as a endothelial lineage, a smooth muscle lineage or a cardiac lineage. In particular, one embodiment present invention relates to methods to induce a cell to enter the Isl1 + lineage by inhibiting a wnt signalling pathway in the cell. Another aspect of the present invention relates to methods to expand a cell of the Isl1 + lineage, such as a Isl1 + progenitor by activating a wnt signalling pathway in the Isl1 + progenitor. Another aspect of the present invention relates to use of cells of the isl1 + lineage in subjects for therapeutic and preventative treatment of cardiovascular diseases.

Abstract translation: 本发明涉及用于诱导和细胞进入胰岛1（Isl1 + / /）谱系的方法和用于扩增胰岛1 +细胞的细胞的方法， 谱系。 本发明的一个方面涉及诱导细胞进入胰岛血清谱系的方法，更具体地涉及诱导细胞进入伊斯兰+ 成为可以沿着多种不同谱系（如内皮细胞谱系，平滑肌谱系或心脏谱系）分化的Isl1 + + / / SUP>祖细胞系。 特别地，本发明的一个实施方案涉及通过抑制细胞中的wnt信号传导途径来诱导细胞进入Isl1 + / / s谱系的方法。 本发明的另一方面涉及通过在Isl1 SUP中激活wnt信号传导途径来扩展Isl1 + / / pL谱系的细胞，例如Isl1 + + /祖细胞的方法 > + 祖先。 本发明的另一方面涉及在患有治疗和预防性治疗心血管疾病的受试者中使用isl1 + / / p>谱系的细胞。