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AssigneeYale University
InventorsSpyridon Artavanis-Tsakonas, Mark Edward Fortini, Kenji Matsuno
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The present invention is directed to methods for the expansion of non-terminally differentiated cells ("precursor cells") using agonists of Notch function, by inhibiting the differentiation of the cells without inhibiting proliferation (mitotic activity) such that an expanded population of non-terminally differentiated cells is obtained. The cells are preferably stem or progenitor cells. These expanded cells can be used in cell replacement therapy to provide desired cell populations and help in the regeneration of diseased and/or injured tissues. The expanded cell populations can also be made recombinant and used for gene therapy, or can be used to supply functions associated with a particular precursor cell or its progeny cell.
A method for expansion of a human precursor cell comprising contacting the cell in vitro with an amount of an agonist of Notch function effective to inhibit differentiation of the cell, and exposing the cell in vitro to cell growth conditions such that the cell proliferates.
A method for expansion of a precursor cell comprising contacting the cell in vitro with an amount of a soluble agonist of Notch function effective to inhibit differentiation of the cell, and exposing the cell in vitro to cell growth conditions such that the cell proliferates.
A method for expansion of a precursor cell comprising recombinantly expressing within the cell an amount of a Deltex protein or fragment thereof which binds to a Notch protein effective to inhibit differentiation of the cells;
A method for expansion of a hematopoietic precursor cell comprising recombinantly expressing within the cell an amount of a Notch protein consisting essentially of the intracellular domain of a Notch protein effective to inhibit differentiation;
A method for expansion of an epithelial precursor cell comprising recombinantly expressing within the cell an amount of a Notch protein consisting essentially of the intracellular domain of a Notch protein effective to inhibit differentiation;
A method for expansion of a liver precursor cell comprising recombinantly expressing within the cell an amount of a Notch protein consisting essentially of the intracellular domain of a Notch protein effective to inhibit differentiation;
A method for expansion of a human precursor cell comprising contacting the precursor cell in vitro with a second cell wherein the second cell recombinantly expresses on its surface a molecule consisting of at least the extracellular domain of a Notch ligand;
A method for expansion of an hematopoietic precursor cell comprising contacting the precursor cell in vitro with a second cell wherein the second cell recombinantly expresses on its surface a molecule consisting of at least the extracellular domain of a Notch ligand;
A method for expansion of a human precursor cell comprising contacting the precursor cell in vitro with an amount of a second cell expressing a Notch ligand effective to inhibit differentiation of the cell;
A method for promoting mammalian neuronal cell growth comprising contacting a mammalian neuron in vitro with an antagonist of Notch function and exposing the neuron in vitro to neuronal cell growth conditions.
A method for expansion of a precursor cell comprising contacting the cell in vitro with an amount of a soluble fragment of a Delta protein effective to inhibit differentiation of the cell, and exposing the cell in vitro to cell growth conditions such that the cell proliferates.
A method for expansion of a precursor cell comprising contacting the cell in vitro with an amount of a soluble fragment of a Serrate protein effective to inhibit differentiation of the cell, and exposing the cell in vitro to cell growth conditions such that the cell proliferates.
Dependencies are inferred from the claim text.