Methods of treating ischemia
AssigneeFate Therapeutics, Inc.
InventorsDan Shoemaker, Pratik S. Multani, John D. Mendlein, David Robbins
Life of this patent
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Abstract
The invention provides compositions comprising stem and/or progenitor cells that have been treated to enhance the therapeutic properties of the cells for treating ischemia. In particular, the present invention relates to the use of stem and/or progenitor cells having enhanced therapeutic properties to treat an ischemic tissue, a tissue damaged by ischemia, or at least one symptom associated with an ischemic tissue or a tissue damaged by ischemia.
Claims74
A method of increasing stem or progenitor cell homing to an ischemic tissue or a tissue damaged by ischemia, comprising:
- (a) treating stem or progenitor cells ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase CXCR4 gene expression at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells;
- and
- (b) administering a composition comprising the treated stem or progenitor cells to a subject having an ischemic tissue or a tissue damaged by ischemia.
A method of treating a subject having an ischemic tissue or a tissue damaged by ischemia comprising:
- administering a therapeutically effective amount of a composition comprising stem or progenitor cells treated ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase CXCR4 gene expression at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells.
A method of ameliorating at least one symptom associated with an ischemic tissue or a tissue damaged by ischemia in a subject comprising:
- administering a therapeutically effective amount of a composition comprising stem or progenitor cells treated ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase CXCR4 gene expression at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells.
A method of increasing stem or progenitor cell homing to an ischemic tissue or a tissue damaged by ischemia, comprising:
- (a) treating stem or progenitor cells ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase the percent (%) migration in an SDF-1 transwell migration assay at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells;
- and
- (b) administering a composition comprising the treated stem or progenitor cells to a subject having an ischemic tissue or a tissue damaged by ischemia.
A method of treating a subject having an ischemic tissue or a tissue damaged by ischemia comprising:
- administering a therapeutically effective amount of a composition comprising stem or progenitor cells treated ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase the percent (%) migration in an SDF-1 transwell migration assay at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells.
A method of ameliorating at least one symptom associated with an ischemic tissue or a tissue damaged by ischemia in a subject comprising:
- administering a therapeutically effective amount of a composition comprising stem or progenitor cells treated ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase the percent (%) migration in an SDF-1 transwell migration assay at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells.
A method of ameliorating at least one symptom associated with ischemia in a subject comprising:
- administering to a subject in need thereof, a therapeutically effective amount of a composition comprising hematopoietic stem and progenitor cells that have been contacted ex vivo with 16, 16-dmPGE2 or PGE2 at a temperature of about 37° C. for a time of about two hours;
- wherein the gene expression of one or more genes selected from the group consisting of:
- hyaluronan synthase 1 (HAS1), GTP-binding protein GEM (GEM), dual specificity protein phosphatase 4 (DUSP4), amphiregulin (AREG), Nuclear receptor related 1 protein (NR4A2), renin (REN), cAMP-responsive element modulator (CREM), collagen, type I, alpha 1 (COL1A1), Fos-related antigen 2 (FOSL2), or CXC chemokine receptor 4 (CXCR4) is increased by at least five fold in the contacted hematopoietic stem or progenitor cells compared to the expression of the genes in non-contacted hematopoietic stem or progenitor cells.
A method of ameliorating at least one symptom associated with ischemia in a subject comprising:
- administering to a subject in need thereof, a therapeutically effective amount of a composition comprising hematopoietic stem and progenitor cells that have been contacted ex vivo with (i) 16, 16-dmPGE2 or PGE2 and (ii) a glucocorticoid selected from the group consisting of medrysone, hydrocortisone, alclometasone, dexamethasone, methylprednisolone, triamcinolone or Cortisol, at a temperature of about 37° C. for a time of about two hours;
- wherein the gene expression of one or more genes selected from the group consisting of:
- hyaluronan synthase 1 (HAS1), GTP-binding protein GEM (GEM), dual specificity protein phosphatase 4 (DUSP4), amphiregulin (AREG), Nuclear receptor related 1 protein (NR4A2), renin (REN), cAMP-responsive element modulator (CREM), collagen, type I, alpha 1 (COL1A1), Fos-related antigen 2 (FOSL2), or CXC chemokine receptor 4 (CXCR4) is increased by at least five fold in the contacted hematopoietic stem or progenitor cells compared to the expression of the genes in non-contacted hematopoietic stem or progenitor cells.
A method of treating an ischemic tissue in a subject comprising:
- administering to a subject in need thereof, a therapeutically effective amount of a composition comprising hematopoietic stem and progenitor cells that have been contacted ex vivo with 16, 16-dmPGE2 or PGE2 at a temperature of about 37° C. for a time of about two hours;
- wherein the gene expression of one or more genes selected from the group consisting of:
- hyaluronan synthase 1 (HAS1), GTP-binding protein GEM (GEM), dual specificity protein phosphatase 4 (DUSP4), amphiregulin (AREG), Nuclear receptor related 1 protein (NR4A2), renin (REN), cAMP-responsive element modulator (CREM), collagen, type I, alpha 1 (COL1A1), Fos-related antigen 2 (FOSL2), or CXC chemokine receptor 4 (CXCR4) is increased by at least five fold in the contacted hematopoietic stem or progenitor cells compared to the expression of the genes in non-contacted hematopoietic stem or progenitor cells.
A method of treating an ischemic tissue in a subject comprising:
- administering to a subject in need thereof, a therapeutically effective amount of a composition comprising hematopoietic stem and progenitor cells that have been contacted ex vivo with (i) 16, 16-dmPGE2 or PGE2, and (ii) a glucocorticoid selected from the group consisting of medrysone, hydrocortisone, alclometasone, dexamethasone, methylprednisolone, triamcinolone or Cortisol, at a temperature of about 37° C. for a time of about two hours;
- wherein the gene expression of one or more genes selected from the group consisting of:
- hyaluronan synthase 1 (HAS1), GTP-binding protein GEM (GEM), dual specificity protein phosphatase 4 (DUSP4), amphiregulin (AREG), Nuclear receptor related 1 protein (NR4A2), renin (REN), cAMP-responsive element modulator (CREM), collagen, type I, alpha 1 (COL1A1), Fos-related antigen 2 (FOSL2), or CXC chemokine receptor 4 (CXCR4) is increased by at least fifty fold in the contacted hematopoietic stem or progenitor cells compared to the expression of the genes in non-contacted hematopoietic stem or progenitor cells.
Dependencies are inferred from the claim text.