Modulation of splenocytes in cell therapy

Abstract

The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that have one or more of the following effects in an injured subject: interact with splenocytes, preserve splenic mass, increase proliferation of CD4+ and CD8+ T-cells, increase IL-4 and IL-10, decrease IL-6 and IL-1β, and increase M2:M1 macrophage ratio at the site of injury. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to have these effects. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency for achieving these effects.

1 - 16 . (canceled) 
     
     
         17 . A method for treating demyelination in a subject with a demyelinating disease, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to treat the demyelinating disease, isolated, expanded human multipotent non-embryonic, non-germ cells that can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages, are allogeneic or xenogeneic to the subject; wherein no immunosuppressant is used adjunctively to said cells. 
     
     
         18 . A method for treating demyelination in a subject with a demyelinating disease, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to treat the demyelinating disease, isolated, expanded human multipotent non-embryonic, non-germ cells that express telomerase and are allogeneic or xenogeneic to the subject; wherein no immunosuppressant is used adjunctively to said cells. 
     
     
         19 . A method for treating demyelination in a subject with a demyelinating disease, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to treat the demyelinating disease, isolated, expanded human multipotent non-embryonic, non-germ cells that are positive for oct3/4 and are allogeneic or xenogeneic to the subject; wherein no immunosuppressant is used adjunctively to said cells. 
     
     
         20 . A method for treating demyelination in a subject with a demyelinating disease, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to treat the demyelinating disease, isolated, expanded human multipotent non-embryonic, non-germ cells that have undergone at least 40 cell doublings in culture prior to their use, and are allogeneic or xenogeneic to the subject; wherein no immunosuppressant is used adjunctively to said cells. 
     
     
         21 . A method according to  claim 18 , wherein said cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages. 
     
     
         22 . A method according to  claim 19 , wherein said cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages. 
     
     
         23 . A method according to  claim 20 , wherein said cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages. 
     
     
         24 . A method according to  claim 19 , wherein said cells express telomerase. 
     
     
         25 . A method according to  claim 20 , wherein said cells express telomerase. 
     
     
         26 . The method according to  claim 20 , wherein said cells are positive for oct 3/4. 
     
     
         27 . The method according to  claim 17 , wherein said cells express telomerase and are positive for oct 34/. 
     
     
         28 . A method according to  claim 17 , wherein said cells express telomerase and have undergone at least 40 cell doublings prior to their use. 
     
     
         29 . A method according to  claim 17 , wherein said cells express oct 3/4 and have undergone at least 40 cell doublings prior to their use. 
     
     
         30 . A method according to  claim 18 , wherein said cells express oct 3/4 and have undergone at least 40 cell doublings prior to their use. 
     
     
         31 . A method according to  claim 17 , wherein said cells express telomerase, are positive for oct 3/4 and have undergone at least 40 cell doublings prior to their use. 
     
     
         32 . A method according to  claim 17 , wherein said cells are derived from bone marrow. 
     
     
         33 . A method according to  claim 31 , wherein said cells are derived from bone marrow. 
     
     
         34 . A method according to  claim 32 , wherein the demyelinating disease is selected from multiple sclerosis, Guillain-Barre syndrome, and systemic lupus erythematosus. 
     
     
         35 . A method according to claim  15 , wherein the demyelinating disease is selected from multiple sclerosis, Guillain-Barre syndrome, and systemic lupus erythematosus. 
     
     
         36 . A method according to  claim 32 , wherein one or more doses of 104 to 108 of said cells per kilogram of the subject's mass are used. 
     
     
         37 . A method according to  claim 33 , wherein one or more doses of 104 to 108 of said cells per kilogram of the subject's mass are used. 
     
     
         38 . A method according to  claim 34 , wherein one or more doses of 104 to 108 of said cells per kilogram of the subject's mass are used. 
     
     
         39 . A method according to  claim 35 , wherein one or more doses of 104 to 108 of said cells per kilogram of the subject's mass are used. 
     
     
         40 . A method according to  claim 32 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         41 . A method according to  claim 33 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         42 . A method according to  claim 34 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         43 . A method according to  claim 35 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         44 . A method according to  claim 32  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         45 . A method according to  claim 33  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         46 . A method according to  claim 34  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         47 . A method according to  claim 35  wherein said cells are administered by an intravenous or other parenteral method.