Enhanced stem cell composition

Abstract

The invention provides improved methods for cell therapy. In particular, the invention provides therapeutic compositions of enhanced hematopoietic stem and progenitor cells having improved engraftment and homing properties, and methods of making the therapeutic compositions. The invention further provides methods of improving the efficacy of hematopoietic stem and progenitor cell transplantation including transplanting the therapeutic composition to subjects in need of hematopoietic system reconstitution.

1 - 162 . (canceled) 
     
     
         163 . A cell graft comprising a hematopoietic stem or progenitor cell, wherein the hematopoietic stem or progenitor cell has at least 30-fold greater gene expression of CXCR4 compared to basal CXCR4 gene expression of a control hematopoietic stem or progenitor cell. 
     
     
         164 . The cell graft of  claim 163 , wherein the hematopoietic stem or progenitor cell has at least 40-, 50-, 60-, 70-, or 80-fold greater CXCR4 gene expression compared to basal CXCR4 gene expression. 
     
     
         165 . The cell graft of  claim 163 , wherein the hematopoietic stem or progenitor cell is a population of hematopoietic stem and progenitor cells. 
     
     
         166 . The cell graft of  claim 165 , wherein the population comprises;
 (a) (i) about 0.1%, 0.5%, 1%, 2%, 5%, 10%, 15%, 20%, 25%, or 30% hematopoietic stem or progenitor cells, or
 (ii) about 1% to about 3%, about 70% to about 80%, or about 95% to about 100% hematopoietic stem or progenitor cells; or 
   (b) (i) less than about 0.10, 0.50, 1.0, 3, 5, 10, 15, 20, or 30% CD34+ cells,
 (ii) at least about 0.01% and no more than about 50% CD34+ cells, or 
 (iii) at least about 1% CD34+ cells, at least about 3% CD34+ cells, at least about 5% CD34+ cells, at least about 90% CD34+ cells, or at least about 95% CD34+ cells. 
   
     
     
         167 . The cell graft of  claim 166 , wherein the cells are ready for administration to a human subject in need thereof. 
     
     
         168 . The cell graft of  claim 166 , wherein the hematopoietic stem or progenitor cell is a component of a therapeutic composition. 
     
     
         169 . The cell graft of  claim 166 , wherein the hematopoietic stem or progenitor cell has been obtained from bone marrow, umbilical cord blood, mobilized peripheral blood, Wharton's jelly, placenta, fetal blood, or induced pluripotent stem cells (iPSCs). 
     
     
         170 . A composition comprising a cell graft for use in treating a subject in need of cell therapy, wherein the cell graft comprises a hematopoietic stem or progenitor cell, wherein the hematopoietic stem or progenitor cell has at least 30-fold greater gene expression of CXCR4 compared to basal CXCR4 gene expression of a control hematopoietic stem or progenitor cell. 
     
     
         171 . The composition of  claim 170  wherein:
 (a) the subject has acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), juvenile myelomonocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, severe aplastic anemia, Fanconi's anemia, paroxysmal nocturnal hemoglobinuria (PNH), pure red cell aplasia, amegakaryocytosis/congenital thrombocytopenia, severe combined immunodeficiency syndrome (SCID), Wiskott-Aldrich syndrome, beta-thalassemia major, sickle cell disease, Hurler's syndrome, adrenoleukodystrophy, metachromatic leukodystrophy, myelodysplasia, refractory anemia, chronic myelomonocytic leukemia, agnogenic myeloid metaplasia, familial erythrophagocytic lymphohistiocytosis, solid tumors, chronic granulomatous disease, mucopolysaccharidoses, or Diamond Blackfan; 
 (b) the subject has breast cancer, ovarian cancer, brain cancer, prostate cancer, lung cancer, colon cancer, skin cancer, liver cancer, pancreatic cancer, or sarcoma; 
 (c) the subject has received bone marrow ablative or non-myeloablative chemotherapy or radiation therapy; 
 (d) the subject is a bone marrow donor; or 
 (e) the subject has at least one symptom associated with an ischemic tissue or a tissue damaged by ischemia,
 wherein the ischemia 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, 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, and wounds to tissues or organs. 
 
 
     
     
         172 . The composition  claim 170 , wherein the subject is a human subject. 
     
     
         173 . A composition comprising the cell graft of  claim 170  for use in the treatment of an immunological disease or disorder in a subject. 
     
     
         174 . The composition of  claim 170 , wherein the composition is for use in the treatment of a cancer in a subject. 
     
     
         175 . The composition of  claim 170 , wherein the subject has breast cancer, ovarian cancer, brain cancer, prostate cancer, lung cancer, colon cancer, skin cancer, liver cancer, pancreatic cancer, or sarcoma. 
     
     
         176 . The composition of  claim 170 , wherein the subject has received bone marrow ablative or nonmyeloablative chemotherapy or radiation therapy.