MESENCHYMAL STEM CELLS EXPRESSING TNF-ALPHA RECEPTORS
Mesenchymal stem cells which express TNF-α receptor Type I in an amount of at least 13 pg/10 6 cells. Such mesenchymal stem cells inhibit the proliferation of lymphocytes and may be employed, in particular, in the treatment of graft-versus-host disease.
1 - 5 . (canceled)
6 . A method of treating a disease or disorder involving an immunological response in a subject comprising administering to the subject a population of mesenchymal stem cells that has been selected based on expression of TNF-α receptor Type I in an amount of at least 13 pg/10 6 cells.
7 . The method of claim 6 , wherein the mesenchymal stem cells express TNF-α receptor Type I in an amount of at least 15 pg/10 6 cells.
8 . The method of claim 6 , wherein the mesenchymal stem cells express TNF-α receptor Type I in an amount of at least 18 pg/10 6 cells.
9 . The method of claim 6 , further comprising selecting the population of mesenchymal stem cells expressing TNF-α receptor Type I in an amount of at least 13 pg/10 6 cells
10 . The method of claim 6 , wherein the immunological response is associated with an autoimmune disease.
11 . The method of claim 10 , where the autoimmune disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, Type I diabetes, Crohn's disease, Guillain-Barré syndrome, lupus erythematosus, myasthenia gravis, optic neuritis, psoriasis, Graves' disease, Hashimoto's disease, Ord's thyroiditis, aplastic anemia, Reiter's syndrome, autoimmune hepatitis, primary biliary cirrhosis, antiphospholipid antibody syndrome, opsoclonus myoclonus syndrome, temporal arteritis, acute disseminated encephalomyelitis, Goodpasture's syndrome, Wegener's granulomatosis, coeliac disease, pemphigus, polyarthritis, warm autoimmune hemolytic anemia, and scleroderma.
12 . The method of claim 6 , wherein the immunological response is associated with graft versus host disease.
13 . The method of claim 6 , wherein TNF-α receptor Type I expression is determined using an enzyme-linked immunosorbent assay.
14 . The method of claim 6 , wherein the donor is a human donor.
15 . The method of claim 6 , wherein the mesenchymal stem cells are administered by intravenous, intraarterial, or intraperitoneal administration.
16 . The method of claim 6 , wherein the administering of an effective amount of the mesenchymal stem cells to the subject suppresses peripheral blood mononuclear cell (PBMC) proliferation.
17 . The method of claim 16 , wherein the PBMCs are CD3/CD28-induced PBMCs.
18 . The method of claim 6 , wherein the population of mesenchymal stem cells is frozen at about −80° C. before administering to the subject.
19 . The method of claim 18 , wherein the population of mesenchymal stem cells undergoes more than one freeze-thaw cycle.
20 . A method of obtaining mesenchymal stem cells which express TNF-α receptor Type I in an amount of at least 13 pg/10 6 cells, comprising selecting mesenchymal stem cells which express TNF-α receptor Type I in an amount of at least 13 pg/10 6 cells in at least one cell population obtained from at least one donor.
21 . The method of claim 20 , wherein said selected mesenchymal stem cells express TNF-α receptor Type I in an amount of at least 15 pg/10 6 cells.
22 . The method of claim 20 , wherein said selected mesenchymal stem cells express TNF-α receptor Type I in an amount of at least 18 pg/10 6 cells.
23 . The method of claim 20 , wherein TNF-α receptor Type I expression is determined using an enzyme-linked immunosorbent assay.
24 . The method of claim 20 , wherein the donor is a human donor.
25 . The method of claim 6 , wherein the mesenchymal stem cells are obtained from a sample selected from the group consisting of adherent marrow, periosteal cells, blood, skin, cord blood, muscle, fat, bone, or perichondrium.