Methods of treating ischemia

Patent metadata

Field	Value
Publication number	US-10980838-B2
Application number	US-201816135889-A
Country	US
Kind code	B2
Filing date	Sep 19, 2018
Priority date	Dec 2, 2011
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

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.

First claim

We claim:

1. A method of increasing recruitment of endogenous cells to a damaged tissue comprising:
(a) treating stem or progenitor cells ex vivo with a prostaglandin pathway agonist and a glucocorticoid; and
(b) intravascularly administering a composition comprising the treated stem or progenitor cells to a subject having damaged tissue.

2. The method according to claim 1 , wherein endogenous cells are stem cells and endothelial progenitor cells.

3. The method according to claim 1 , wherein the stem or progenitor cells localize to a site of tissue damage in vivo.

4. The method according to claim 1 , wherein the administration is intravenous.

5. The method according to claim 1 , further comprising ex vivo treatment with a phosphodiesterase type 4 inhibitor.

6. The method according to claim 1 , wherein the treatment of the stem or progenitor cells is 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.

7. The method according to claim 1 , wherein:
a) the stem or progenitor cells have been treated at a temperature of about 22° C. to about 37° C. for a period of time of less than about 24 hours;
b) the stem or progenitor cells have been treated at a temperature of about 22° C. to about 37° C. for a time of about one to about four hours; or
c) the stem or progenitor cells have been treated at a temperature of about 37° C. for a time of about 4 hours.

8. The method according to claim 1 , wherein:
a) the stem or progenitor cells are embryonic stem cells;
b) the stem or progenitor cells are adult stem cells;
c) the stem or progenitor cells are selected from the group consisting of: endothelial stem or progenitor cells, mesodermal stem or progenitor cells, and ectodermal stem or progenitor cells;
d) the stem or progenitor cells are selected from the group consisting of: mesenchymal stem or progenitor cells, hematopoietic stem or progenitor cells, placental stem or progenitor cells, umbilical cord stem or progenitor cells, bone marrow stem cells, and Wharton's jelly stem or progenitor cells;
e) the stem or progenitor cells are hematopoietic stem or progenitor cells;
f) the stem or progenitor cells are isolated from peripheral blood, bone marrow, umbilical cord blood, Wharton's jelly, placenta, or fetal blood;
g) the stem or progenitor cells are CD34+ cells;
h) the stem or progenitor cells are, or have been, expanded ex vivo prior to the treatment of the cells;
i) the stem or progenitor cells are allogeneic or autologous;
j) the stem or progenitor cells are allogeneic and have a complete or partial HLA-match with the subject;
k) the stem or progenitor cells are not matched with the subject;
l) the stem or progenitor cells are xenogeneic; or
m) the stem or progenitor cells are washed to substantially remove the prostaglandin pathway agonist or glucocorticoid in the composition, prior to administration of the composition to the subject.

9. The method according to claim 1 , wherein:
a) the prostaglandin pathway agonist is selected from the group consisting of: a prostaglandin, a prostaglandin EP2 receptor agonist, a prostaglandin EP4 receptor agonist and an agent having 16,16-dimethyl PGE2 (dmPGE2) activity;
b) the prostaglandin pathway agonist is selected from the group consisting of: prostaglandin E 2 (PGE 2 ), and dmPGE 2 ;
c) the glucocorticoid is selected from the group consisting of: alclometasone, alclometasone dipropionate, amcinonide, beclometasone, beclomethasone dipropionate, betamethasone, betamethasone benzoate, betamethasone valerate, budesonide, ciclesonide, clobetasol, clobetasol butyrate, clobetasol propionate, clobetasone, clocortolone, cloprednol, cortisol, cortisone, cortivazol, deflazacort, desonide, desoxycortone, desoxymethasone, dexamethasone, diflorasone, diflorasone diacetate, diflucortolone, diflucortolone valerate, difluorocortolone, difluprednate, fluclorolone, fluclorolone acetonide, fludroxycortide, flumethasone, flumethasone pivalate, flunisolide, flunisolide hemihydrate, fluocinolone, fluocinolone acetonide, fluocinonide, fluocortin, fluocoritin butyl, fluocortolone, fluorocortisone, fluorometholone, fluperolone, fluprednidene, fluprednidene acetate, fluprednisolone, fluticasone, fluticasone propionate, formocortal, halcinonide, halometasone, hydrocortisone, hydrocortisone acetate, hydrocortisone aceponate, hydrocortisone buteprate, hydrocortisone butyrate, loteprednol, medrysone, meprednisone, 6a-methylprednisolone, methylprednisolone, methylprednisolone acetate, methylprednisolone aceponate, mometasone, mometasone furoate, mometasone furoate monohydrate, paramethasone, prednicarbate, prednisolone, prednisone, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide and ulobetasol;
d) the glucocorticoid is selected from the group consisting of: medrysone, hydrocortisone, alclometasone, dexamethasone, methylprednisolone, triamcinolone or Cortisol; or
e) the prostaglandin pathway agonist is PGE 2 or dmPGE 2 or an analogue thereof, and the glucocorticoid is medrysone or dexamethasone.

10. The method according to claim 6 , wherein the % migration of the treated cells in an SDF-1 transwell migration assay is increased at least three fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells.

11. The method according to claim 1 , wherein:
a) the damaged tissue is associated with acute coronary syndrome, acute lung injury (ALI), acute myocardial infarction (AMI), acute respiratory distress syndrome (ARDS), arterial occlusive disease, arteriosclerosis, articular cartilage defect, aseptic systemic inflammation, atherosclerotic cardiovascular disease, autoimmune disease, bone fracture, bone fracture, brain edema, brain hypoperfusion, Buerger's disease, burns, cancer, cardiovascular disease, cartilage damage, cerebral infarct, cerebral ischemia, cerebral stroke, cerebrovascular disease, chemotherapy-induced neuropathy, chronic infection, chronic mesenteric ischemia, claudication, congestive heart failure, connective tissue damage, contusion, coronary artery disease (CAD), critical limb ischemia (CLI), Crohn's disease, deep vein thrombosis, deep wound, delayed ulcer healing, delayed wound-healing, diabetes (type I and type II), diabetic neuropathy, diabetes induced ischemia, disseminated intravascular coagulation (DIC), embolic brain ischemia, frostbite, graft-versus-host disease, hereditary hemorrhagic telengiectasiaischemic vascular disease, hyperoxic injury, hypoxia, inflammation, inflammatory bowel disease, inflammatory disease, injured tendons, intermittent claudication, intestinal ischemia, ischemia, ischemic brain disease, ischemic heart disease, ischemic peripheral vascular disease, ischemic placenta, ischemic renal disease, ischemic vascular disease, ischemic-reperfusion injury, laceration, left main coronary artery disease, limb ischemia, lower extremity ischemia, myocardial infarction, myocardial ischemia, organ ischemia, osteoarthritis, osteoporosis, osteosarcoma, Parkinson's disease, peripheral arterial disease (PAD), peripheral artery disease, peripheral ischemia, peripheral neuropathy, peripheral vascular disease, pre-cancer, pulmonary edema, pulmonary embolism, remodeling disorder, renal ischemia, retinal ischemia, retinopathy, sepsis, skin ulcers, solid organ transplantation, spinal cord injury, stroke, subchondral-bone cyst, thrombosis, thrombotic brain ischemia, tissue ischemia, transient ischemic attack (TIA), traumatic brain injury, ulcerative colitis, vascular disease of the kidney, vascular inflammatory conditions, von Hippel-Lindau syndrome, or wound

Assignees

• Fate Therapeutics Inc

Inventors

• Shoemaker Dan
• Multani Pratik S
• Mendlein John D
• Robbins David

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• C12N2501/39

  Steroid hormones · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/16

  Central respiratory analeptics · CPC title