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Ex vivo progenitor and stem cell expansion for use in the treatment of disease of endodermally-derived organs

  • US 20070082397A1
  • Filed: 07/15/2004
  • Published: 04/12/2007
  • Est. Priority Date: 07/17/2003
  • Status: Abandoned Application
First Claim
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1. A method of enhancing function of an endodermally derived organ in a subject in need thereof, the method comprising:

  • (a) obtaining a population of cells comprising stem and/or progenitor cells;

    (b) culturing said stem and/or progenitor cells ex-vivo under conditions allowing for cell proliferation and, at the same time, culturing said cells under conditions selected from the group consisting of;

    (i) conditions reducing expression and/or activity of CD38 in said cells;

    (ii) conditions reducing capacity of said cells in responding to signaling pathways involving CD38 in said cells;

    (iii) conditions reducing capacity of said cells in responding to retinoic acid, retinoids and/or Vitamin D in said cells;

    (iv) conditions reducing capacity of said cells in responding to signaling pathways involving the retinoic acid receptor, the retinoid X receptor and/or the Vitamin D receptor in said cells;

    (v) conditions reducing capacity of said cells in responding to signaling pathways involving PI 3-kinase;

    (vi) conditions wherein said cells are cultured in the presence of nicotinamide, a nicotinamide analog, a nicotinamide or a nicotinamide analog derivative or a nicotinamide or a nicotinamide analog metabolite;

    (vii) conditions wherein said cells are cultured in the presence of a copper chelator;

    (viii) conditions wherein said cells are cultured in the presence of a copper chelate;

    (ix) conditions wherein said cells are cultured in the presence of a PI 3-kinase inhibitor;

    thereby expanding the stem and/or progenitor cells while at the same time, substantially inhibiting differentiation of the stem and/or progenitor cells ex-vivo; and

    (c) implanting said cells in an endodermally-derived organ of the subject.

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