公开(公告)号：US20230332108A1

公开(公告)日：2023-10-19

申请号：US18181889

申请日：2023-03-10

Applicant: University Health Network

Inventor： Gordon Keller ,  Blair Kenneth Gage

IPC: A61P1/16 ,  C12N5/071

CPC classification number: C12N5/069 ,  A61P1/16 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2506/45

Abstract: This disclosure describes vascular endothelial cells (VECs) and liver sinusoidal endothelial cells (LSECs), and methods and compositions for producing such cells.

公开(公告)号：US11730770B2

公开(公告)日：2023-08-22

申请号：US16737768

申请日：2020-01-08

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Gordon Keller ,  Stephanie Protze

IPC: A61K35/34 ,  C12N5/077 ,  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.

公开(公告)号：US20220233605A1

公开(公告)日：2022-07-28

申请号：US17616522

申请日：2020-06-03

Applicant: University Health Network

Inventor： Shinichiro Ogawa ,  Mina Ogawa ,  Gordon Keller

IPC: A61K35/407 ,  C12N5/071 ,  A01N1/02 ,  G01N33/50 ,  A61K35/413 ,  A61P1/16

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

公开(公告)号：US10736923B2

公开(公告)日：2020-08-11

申请号：US15977536

申请日：2018-05-11

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Gordon Keller ,  April M. Craft

IPC: C12N5/077 ,  G01N33/50 ,  A61K35/32

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.

公开(公告)号：US12129490B2

公开(公告)日：2024-10-29

申请号：US16109202

申请日：2018-08-22

Applicant: UNIVERSITY HEALTH NETWORK ,  THE HOSPITAL FOR SICK CHILDREN

Inventor： Gordon Keller ,  Shinichiro Ogawa ,  Anand Ghanekar ,  Christine Bear ,  Binita M. Kamath ,  Mina Ogawa ,  James Surapisitchat

IPC: C12N5/071 ,  A61K35/407

CPC classification number: C12N5/067 ,  C12N5/0679 ,  A61K35/407 ,  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.

公开(公告)号：US20190322986A1

公开(公告)日：2019-10-24

申请号：US15977505

申请日：2018-05-11

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Gordon Keller ,  April M. Craft ,  Nicole C. Dubois

IPC: C12N5/077 ,  C12Q1/6881

Abstract: The present invention relates to in vitro methods of enriching populations of human pluripotent stem cells that are induced to differentiate to cardiomyocyte progenitor cells and cardiomyocyte cells. The cell populations can be enriched by isolating cells that express SIRPA. The invention also related to in vitro-enriched populations of cardiomyocyte cells and cardiomyocyte progenitor cells obtained from populations of pluripotent stem.

公开(公告)号：US09834754B2

公开(公告)日：2017-12-05

申请号：US14359517

申请日：2012-11-21

Applicant: University Health Network ,  Sunnybrook Research Institute

Inventor： Gordon Keller ,  Juan Carlos Zuniga-Pflucker ,  Marion J. Kennedy ,  Christopher Michael Sturgeon ,  Andrea Ditadi ,  Geneve Sheandra Awong

IPC: C12N5/00 ,  C12N5/0789 ,  G01N33/569

CPC classification number: C12N5/0647 ,  C12N2500/24 ,  C12N2500/35 ,  C12N2500/38 ,  C12N2501/105 ,  C12N2501/115 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/165 ,  C12N2501/2303 ,  C12N2501/2306 ,  C12N2501/2307 ,  C12N2501/2311 ,  C12N2501/26 ,  C12N2502/1394 ,  C12N2506/02 ,  C12N2506/45 ,  G01N33/56972 ,  G01N2333/70596

Abstract: There is described herein a method of enriching a population of stem cells for hematopoietic progenitors. The method comprises inducing hematopoietic differentiation in a population of human embryonic stem cells or human induced pluripotent stem cells; sorting the population based on expression of CD43 and at least one of CD34, CD31 and CD144; and selecting a fraction that is at least one of CD34+CD43−, CD31+CD43− and CD144+CD43−. Also provided are populations of hematopoietic progenitors obtained by the methods described herein.

公开(公告)号：US20150104430A1

公开(公告)日：2015-04-16

申请号：US14397657

申请日：2013-04-30

Applicant: University Health Network

Inventor： Gordon Keller ,  Maria Cristina Nostro ,  Audrey Holtzinger ,  Farida Sarangi

IPC: C12N5/071 ,  A61K35/39

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：US10561687B2

公开(公告)日：2020-02-18

申请号：US15550572

申请日：2016-02-17

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Gordon Keller ,  Stephanie Protze

IPC: C12N5/00 ,  A61K35/34 ,  C12N5/077 ,  C12N5/10

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.

公开(公告)号：US20190336537A1

公开(公告)日：2019-11-07

申请号：US16466278

申请日：2017-12-04

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Gordon Keller ,  Stephanie Protze ,  Jee Hoon Lee

IPC: A61K35/28 ,  A61K35/34 ,  G01N33/50 ,  G01N33/68 ,  A61P9/04 ,  C12N5/077

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.