Methods and compositions for modulating angiogenesis and vasculogenesis
AssigneeSanBio, Inc.
InventorsMonique Dao, Ciara Tate, Casey C. Case
Life of this patent
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Abstract
Disclosed herein are methods and compositions for stimulating angiogenesis, using cells descended from marrow adherent stromal cells that have been transfected with sequences encoding a Notch intracellular domain. Applications of these methods and compositions include treatment of ischemic disorders such as stroke.
Claims21
A method for treating an ischemic disorder in a subject, wherein the ischemic disorder occurs outside the central nervous system, the method comprising:
- administering, to a site of ischemic disorder in the subject that is outside the central nervous system, a therapeutically effective amount of cells, wherein the cells are made by a method comprising:
- (a) providing a culture of mesenchymal stem cells,
- (b) contacting the cell culture of step (a) with a polynucleotide comprising sequences encoding a Notch intracellular domain (NICD) wherein said polynucleotide does not encode a full-length Notch protein,
- (c) selecting cells that comprise the polynucleotide of step (b), and
- (d) further culturing the selected cells of step (c) in the absence of selection and in the absence of trophic factors;
- wherein the cells produce angiogenin, angiopoietin-2 (ANG-2) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) at higher levels than do the mesenchymal stem cells of step (a).
A combination for use in treating an ischemic disorder in a subject, wherein the ischemic disorder occurs outside the central nervous system, wherein the combination comprises:
- (a) a first pro-angiogenic agent comprising cells made by a method comprising:
- (i) providing a culture of mesenchymal stem cells,
- (ii) contacting the cell culture of step (i) with a polynucleotide comprising sequences encoding a Notch intracellular domain (NICD) wherein said polynucleotide does not encode a full-length Notch protein,
- (iii) selecting cells that comprise the polynucleotide of step (ii), and
- (iv) further culturing the selected cells of step (iii) in the absence of selection and in the absence of trophic factors;
- wherein the cells produce angiogenin, angiopoietin-2 (ANG-2) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) at higher levels than do the mesenchymal stem cells of step (i);
- and
- (b) a second pro-angiogenic agent.
Dependencies are inferred from the claim text.