公开(公告)号：WO2014124527A1

公开(公告)日：2014-08-21

申请号：PCT/CA2014/000122

申请日：2014-02-18

Applicant: UNIVERSITY HEALTH NETWORK ,  THE HOSPITAL FOR SICK CHILDREN

Inventor： KELLER, Gordon ,  OGAWA, Shinichiro ,  GHANEKAR, Anand ,  BEAR, Christine ,  KAMATH, Binita M. ,  OGAWA, Mina ,  SURAPISITCHAT, James

IPC: C12N5/071 ,  A61K35/12 ,  A61K35/407 ,  A61P1/16 ,  C12N5/0735 ,  C12Q1/02

CPC classification number: C12N5/067 ,  A61K35/407 ,  C12N5/0679 ,  C12N2501/01 ,  C12N2501/115 ,  C12N2501/119 ,  C12N2501/12 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/237 ,  C12N2501/415 ,  C12N2501/42 ,  C12N2501/724 ,  C12N2501/727 ,  C12N2501/999 ,  C12N2502/00 ,  C12N2502/14 ,  C12N2503/02 ,  C12N2506/02 ,  C12N2506/45

Abstract: Methods for producing hepatocyte and/or cholangiocyte lineage cells from pluripotent stem cells, the method comprising (a) specifying the extended nodal agonist treated induced endodermal cell population to obtain a cell population comprising hepatocyte and/or cholangiocyte progenitors by contacting the extended nodal agonist treated induced endodermal cell population with specification media comprising a FGF agonist and a BMP4 agonist and/or active conjugates and/or fragments thereof; (b) inducing maturation, and optionally further lineage specification and/or expansion of the hepatocyte and/or cholangiocyte progenitors of the cell population to obtain a population comprising hepatocyte lineage cells such as hepatoblasts, hepatocytes and/or cholangiocytes, the inducing maturation step comprising generating aggregates of the cell population. Optionally, the method also comprises activating the cAMP pathway within the aggregates and forming co-aggregates.

Abstract translation: 用于从多能干细胞产生肝细胞和/或胆管细胞谱系细胞的方法，所述方法包括（a）指定延长的淋巴结激动剂治疗的诱导的内胚层细胞群，以通过使经延长的淋巴结激动剂治疗以获得包含肝细胞和/或胆管细胞祖细胞的细胞群 具有包含FGF激动剂和BMP4激动剂和/或其活性缀合物和/或其片段的规范培养基的诱导内胚层细胞群; （b）诱导成熟，以及任选地进一步谱系说明和/或扩增细胞群体的肝细胞和/或胆管细胞祖细胞以获得包含肝细胞谱系细胞如肝母细胞，肝细胞和/或胆管细胞的群体，诱导成熟步骤包括 产生细胞群体的聚集体。 任选地，该方法还包括激活聚集体内的cAMP途径并形成共聚集体。

公开(公告)号：WO2016131137A1

公开(公告)日：2016-08-25

申请号：PCT/CA2016/050142

申请日：2016-02-17

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  PROTZE, Stephanie

IPC: C12N5/077 ,  A61K35/34 ,  A61P9/00 ,  C12N5/071 ,  C12N5/0735 ,  C12N5/10

CPC classification number: A61K35/34 ,  C12N5/0657 ,  C12N5/10 ,  C12N2501/115 ,  C12N2501/15 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/165 ,  C12N2501/385 ,  C12N2501/727 ,  C12N2501/999 ,  C12N2506/02 ,  C12N2506/45

Abstract: Provided are methods for producing compositions comprising a population of cardiomyocytes enriched for or substantially devoid of sinoatrial node-like pacemaker cardiomyocytes (SANLCM) from human pluripotent stem cells (hPSCs), and methods of use thereof.

Abstract translation: 提供了用于生产组合物的方法，所述组合物包含从人多能干细胞（hPSC）富集或基本上不含窦房结起搏器心脏起搏器心肌细胞（SANLCM）的心肌细胞群及其使用方法。

公开(公告)号：WO2014161075A1

公开(公告)日：2014-10-09

申请号：PCT/CA2014/000312

申请日：2014-04-02

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  CRAFT, April M.

IPC: C12N5/077 ,  A61K35/32 ,  A61P19/00 ,  C12N5/073 ,  C12Q1/02 ,  G01N33/48 ,  G01N33/50

CPC classification number: A61K35/32 ,  C12N5/0655 ,  C12N2501/115 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/415 ,  C12N2501/999 ,  C12N2503/02 ,  C12N2506/02 ,  C12N2506/03 ,  G01N33/5044

Abstract: A method for generating chondrocytes and/or cartilage, optionally articular like non-hypertrophic chondrocyte cells and/or cartilage like tissue and/or hypertrophic chondrocyte like cells and/or cartilage like tissue, the method comprising: a. culturing a primitive streak-like mesoderm population, optionally a CD56+, PDGFRalpha+ KDR- primitive streak-like mesoderm population, with a paraxial mesoderm specifying cocktail comprising: i. a FGF agonist; ii. a BMP inhibitor; optionally Noggin, LDN-193189, Dorsomorphin; and iii. optionally one or more of a TGFbeta inhibitor, optionally SB431524; and a Wnt inhibitor, optionally DKK1, IWP2, or XAV939; to specify a paraxial mesoderm population expressing cell surface CD73, CD105 and/or PDGFR-beta; b. generating a chondrocyte precursor population comprising: i. culturing the paraxial mesoderm population expressing CD73, CD105 and/or PDGFR-beta at a high cell density optionally in serum free or serum containing media; ii. culturing the high cell density CD73+, CD105+ and/or PDGFRbeta+ paraxial mesoderm population with a TGFbeta3 agonist in serum free media to produce a high cell density Sox9+, collagen 2+ chondrocyte precursor population; and c. either i. culturing the high cell density Sox9+, collagen 2+ chondrocyte precursor population with the TGFbeta3 agonist for an extended period of time to produce an articular like non-hypertrophic chondrocyte cells and/or cartilage like tissue; or ii. culturing the high cell density Sox9+ collagen2+ chondrocyte precursor population with a BMP4 agonist for an extended period of time to produce a hypertrophic chondrocyte like cells and/or cartilage like tissue.

Abstract translation: 一种用于产生软骨细胞和/或软骨的方法，任选地关节像非增生性软骨细胞和/或软骨样组织和/或肥大软骨细胞样细胞和/或软骨样组织，所述方法包括：a。 培养原始条纹状中胚层群体，任选地具有CD56 +，PDGFRα+ KDR-原始条纹样中胚层群体，其中傍轴中胚层指定混合物，包括：i。 FGF激动剂; II。 BMP抑制剂; 任选地，Noggin，LDN-193189，Dorsomorphin; 和iii。 任选地一种或多种TGFβ抑制剂，任选的SB431524; 和Wnt抑制剂，任选地DKK1，IWP2或XAV939; 指定表达细胞表面CD73，CD105和/或PDGFR-β的近轴中胚层群; 湾 产生软骨细胞前体群体，包括：i。 以高细胞密度任选地在无血清或含血清培养基中培养表达CD73，CD105和/或PDGFR-β的近轴中胚层群; II。 在血清游离培养基中培养具有TGFbeta3激动剂的高细胞密度CD73 +，CD105 +和/或PDGFRβ+近轴中胚层群体以产生高细胞密度Sox9 +，胶原蛋白+2软骨细胞前体种群; 和c。 我是 用TGFbeta3激动剂长时间培养高细胞密度Sox9 +，胶原蛋白+软骨细胞前体种群，以产生关节性非肥大软骨细胞和/或软骨样组织; 或ii。 用BMP4激动剂长时间培养高细胞密度的Sox9 +胶原蛋白2 +软骨细胞前体群体，以产生肥大的软骨细胞样细胞和/或软骨样组织。

公开(公告)号：WO2013163739A1

公开(公告)日：2013-11-07

申请号：PCT/CA2013/000432

申请日：2013-04-30

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  NOSTRO, Maria Cristina ,  HOLTZINGER, Audrey ,  SARANGI, Farida

IPC: C12N5/071 ,  C12N5/02 ,  C12N5/073 ,  C12P21/02

CPC classification number: C12N5/0678 ,  A61K35/39 ,  C12N5/0676 ,  C12N2500/38 ,  C12N2501/11 ,  C12N2501/115 ,  C12N2501/119 ,  C12N2501/155 ,  C12N2501/385 ,  C12N2501/40 ,  C12N2501/415 ,  C12N2502/28 ,  C12N2506/02 ,  C12N2506/45

Abstract: Methods and compositions for producing NKX6-1+ pancreatic progenitor cells and/or insulin producing cells from an endodermal cell population, the method comprising contacting the endodermal cell population with an EGF component, a Nicotinamide component and/or a Noggin component, optionally a combination of at least one EGF component and at least one nicotinamide component to induce the differentiation of at least one endodermal cell into a NKX6-1+ pancreatic progenitor cell, the combination optionally further comprising at least one Noggin component.

Abstract translation: 用于从内胚层细胞群产生NKX6-1 +胰腺祖细胞和/或产生胰岛素的细胞的方法和组合物，所述方法包括使内胚层细胞群体与EGF组分，烟酰胺组分和/或Noggin组分，任选的组合 的至少一种EGF组分和至少一种烟酰胺组分以诱导至少一种内胚层细胞分化成NKX6-1 +胰腺祖细胞，所述组合任选地还包含至少一种Noggin组分。

公开(公告)号：WO2012024782A1

公开(公告)日：2012-03-01

申请号：PCT/CA2011/000965

申请日：2011-08-26

Applicant: UNIVERSITY HEALTH NETWORK ,  KELLER, Gordon ,  CRAFT, April M. ,  DUBOIS, Nicole C.

Inventor： KELLER, Gordon ,  CRAFT, April M. ,  DUBOIS, Nicole C.

IPC: C12N5/077 ,  C12N5/0775 ,  G01N33/567 ,  C12Q1/04 ,  C12Q1/68

CPC classification number: C12N5/0657 ,  C12N2501/115 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/165 ,  C12N2501/415 ,  C12N2506/00 ,  C12N2506/02 ,  C12N2506/45 ,  C12Q1/6881 ,  C12Q2600/158 ,  G01N33/5073 ,  G01N33/53 ,  G01N33/56966

Abstract: The present invention relates to methods for enriching pluripotent stem cell-derived cardiomyocyte progenitor cells and cardiomyocyte cells based on SIRPA expression.

Abstract translation: 本发明涉及基于SIRPA表达富集多能干细胞衍生的心肌细胞祖细胞和心肌细胞的方法。

公开(公告)号：WO2022040798A1

公开(公告)日：2022-03-03

申请号：PCT/CA2021/051181

申请日：2021-08-25

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  ATKINS, Michael

IPC: C12N5/073 ,  A61K35/34 ,  A61K35/407 ,  A61K35/54 ,  A61L27/52 ,  C12N5/02

Abstract: Provided are methods for making yolk sac like hematopoietic progenitors by specifying a KDR+CD235a/b+ mesoderm cells capable of giving rise to T lymphoid lineage cells or cells differentiated therefrom. The method involves contacting pluripotent stem cells (PSCs) with a mesoderm specifying culture composition comprising a BMPR1/R2 agonist, an FGF receptor agonist and an activin receptor agonist to produce a KDR+CD235a/b+ mesoderm cells; and optionally isolating the KDR+CD235a/b+ mesoderm cells.

公开(公告)号：WO2021224885A1

公开(公告)日：2021-11-11

申请号：PCT/IB2021/053915

申请日：2021-05-07

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  MIKRYUKOV, Alexander ,  MAZINE, Amine ,  FERNANDES, Ian

IPC: C12N5/077 ,  A61K35/34 ,  A61K35/44 ,  A61P9/00 ,  A61P9/10 ,  C12N5/071 ,  C12Q1/02 ,  C12Q1/18

Abstract: Methods and compositions for making endocardial cells from pluripotent stemcells are described, as are methods and compositions for using such cells.

公开(公告)号：WO2020058882A1

公开(公告)日：2020-03-26

申请号：PCT/IB2019/057882

申请日：2019-09-18

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  GAGE, Blair Kenneth

IPC: C12N5/071 ,  A61K35/44 ,  A61P1/16 ,  C12N5/073 ,  C12Q1/02 ,  G01N33/15 ,  G01N33/48 ,  G01N33/53

Abstract: Disclosed herein are methods of producing a population of venous angioblast cells from stem cells using a venous angioblast inducing media and optionally isolating a CD34+ population from the cell population comprising the venous angioblast cells, for example using a CD34 affinity reagent, CD31 affinity reagent and/or CD144 affinity reagent, optionally with or without a CD73 affinity reagent as well as methods of further differentiating the venous angioblasts in vitro to produce SEC-LCs and/or in vivo to produce SECs. Uses of the cells and compositions comprising the cells are also described.

公开(公告)号：WO2020245747A1

公开(公告)日：2020-12-10

申请号：PCT/IB2020/055249

申请日：2020-06-03

Applicant: UNIVERSITY HEALTH NETWORK ,  OGAWA, Shinichiro ,  OGAWA, Mina ,  KELLER, Gordon

Inventor： OGAWA, Shinichiro ,  OGAWA, Mina ,  KELLER, Gordon

IPC: C12N5/071 ,  A61K35/407 ,  A61P1/16 ,  C12N5/00

Abstract: Provided herein are methods of making and using a number of different types of liver cells.

公开(公告)号：WO2018098597A1

公开(公告)日：2018-06-07

申请号：PCT/CA2017/051460

申请日：2017-12-04

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon ,  PROTZE, Stephanie ,  LEE, Jee Hoon

IPC: C12N5/077 ,  A61K35/34 ,  A61P9/04 ,  C12N5/071 ,  C12Q1/02 ,  G01N33/48

Abstract: Methods are disclosed for producing populations of cardiomyocytes from pluripotent stem cells. Populations may be enriched for either atrial or ventricular cardiomyocytes and the resulting ventricular population may be essentially free of pacemaker cells. The method includes incubating pluripotent stem cells in a suitable medium with a BMP component, and an activin component, the amounts of activin may be varied to enrich for either atrial or ventricular cardiomyocytes. The enriched populations, as well as methods of using the same to treat patients in need of cardiac repair are disclosed.