Wisconsin Alumni Research Foundation

Procella Therapeutics Ab

Lancell Ab

Xiaojun Lance Lian

Sean Paul Palecek

Timothy Joseph Kamp

Xiaoping Bao

Kenneth R Chien

Samira M Azarin

Jianhua Zhang

Methods for generating high-yield, high-purity epicardial cells are described. Wnt/&#x3b2;-catenin signaling is first activated in human cardiac progenitor cells, by, for example, inhibiting Gsk-3 to induce differentiation into epicardial cells. Methods for long-term in vitro maintenance of human cardiac progenitor cell-derived epicardial cells and method comprising chemically defined, xeno-free, and albumin-free culture conditions are also provided.

Methods for epicardial differentiation of human pluripotent stem cells

Provided is a cell culture medium comprising enriched basal media supplemented with ascorbic acid, a member of the fibroblast growth factor (FGF) superfamily, a transforming growth factor-beta (TGF-beta) superfamily ligand, and a stable glutamine source. Methods of culturing stem cells in such culture medium for extended periods of time, populations of stem cells, and kits are also provided.

Serum-free human pluripotent stem cell culture medium

The present invention provides LIFR and FGFR3 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+ LIFR+ ventricular progenitor cells and/or Islet 1+/FGFR3+ ventricular progenitor cells and/or Islet 1+/LIFR+/FGFR3+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated LIFR+ and/or FGFR3+ ventricular progenitor cells are also provided. Methods of in vivo use of LIFR+ and/or FGFR3+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the LIFR+ and/or FGFR3+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.

Use of LIFR or FGFR3 as a cell surface marker for isolating human cardiac ventricular progenitor cells

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.

Use of jagged 1/frizzled 4 as a cell surface marker for isolating human cardiac ventricular progenitor cells

Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt/&#x3b2;-catenin signaling is first activated in pluripotent cells, by, for example, inhibiting Gsk-3 to obtain a first population of cells. Wnt/&#x3b2;-catenin signaling is then inhibited in the first cell population to induce cardiogenesis. One or more of these steps is performed under defined, albumin-free culture conditions.

Chemically defined albumin-free conditions for cardiomyocyte differentiation of human pluripotent stem cells

Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt/&#x3b2;-catenin signaling is first activated in pluripotent cells, e.g., by inhibition of Gsk-3 to obtain a first population of cells. Wnt/&#x3b2;-catenin signaling is then inhibited in the first cell population to induce cardiogenesis under fully defined, growth factor free culture conditions.

Generation of cardiomyocytes from human pluripotent stem cells

Methods for generating human endothelial cells from human pluripotent stem cells under defined conditions in the absence of VEGF are described. Wnt/&#x3b2;-catenin signaling is activated in human pluripotent stem cells for a defined period, e.g., by inhibition of Gsk3, and then cultured without further exogenous activation of Wnt/&#x3b2;-catenin signaling to obtain a cell population containing human endothelial cells.

Simplified methods for generating endothelial cells from human pluripotent stem cells under defined conditions

Methods for culturing the pluripotent stem cells to undergo epithelial-to-mesenchymal transition and for generating high-yield, high-purity cardiomyocyte cultures from pluripotent stem cells are described. Pluripotent stem cells are cultured on a support with an overlaid matrix and, optionally, exposed to one or more factors to induce epithelial-to-mesenchymal transition and cardiogenesis.

Growing community of inventors

University Park, PA, United States of America

Xiaojun Lance Lian