Immunomodulatory properties of multipotent adult progenitor cells and uses thereof

Abstract

Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.

1 .- 27 . (canceled) 
     
     
         28 . A method for ameliorating an immune dysfunction in a subject suffering from an immune dysfunction, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to ameliorate the dysfunction, 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 the cells have not be genetically engineered to improve their immunological properties. 
     
     
         29 . A method for ameliorating an immune dysfunction in a subject suffering from an immune dysfunction, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to ameliorate the dysfunction, isolated, expanded human multipotent non-embryonic, non-germ cells that express telomerase and are allogeneic or xenogeneic to the subject. 
     
     
         30 . A method for ameliorating an immune dysfunction in a subject suffering from an immune dysfunction, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to ameliorate the dysfunction, isolated, expanded human multipotent non-embryonic, non-germ cells that are positive for oct3/4 and are allogeneic or xenogeneic to the subject; wherein the cells have not been genetically engineered to improve their immunological properties. 
     
     
         31 . A method for ameliorating an immune dysfunction in a subject suffering from an immune dysfunction, said method comprising administering to the subject by an effective route and in a therapeutically effective amount to ameliorate the dysfunction, 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 the cells have not been genetically engineered to improve their immunological properties. 
     
     
         32 . A method according to  claim 29 , 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. 
     
     
         33 . A method according to  claim 30 , 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. 
     
     
         34 . A method according to  claim 31 , 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. 
     
     
         35 . A method according to  claim 30 , wherein said cells express telomerase. 
     
     
         36 . A method according to  claim 31 , wherein said cells express telomerase. 
     
     
         37 . The method according to  claim 31 , wherein said cells are positive for oct 3/4. 
     
     
         38 . The method according to  claim 28 , wherein said cells express telomerase and are positive for oct 34/. 
     
     
         39 . A method according to  claim 28 , wherein said cells express telomerase and have undergone at least 40 cell doublings prior to their use. 
     
     
         40 . A method according to  claim 28 , wherein said cells express oct 3/4 and have undergone at least 40 cell doublings prior to their use. 
     
     
         41 . A method according to  claim 29 , wherein said cells express oct 3/4 and have undergone at least 40 cell doublings prior to their use. 
     
     
         42 . A method according to  claim 28 , wherein said cells express telomerase, are positive for oct3/4 and have undergone at least 40 cell doublings prior to their use. 
     
     
         43 . A method according to  claim 28 , wherein one or more doses of 10 4  to 10 8  of said cells per kilogram of the subject's mass are used. 
     
     
         44 . A method according to  claim 29 , wherein one or more doses of 10 4  to 10 8  of said cells per kilogram of the subject's mass are used. 
     
     
         45 . A method according to  claim 30 , wherein one or more doses of 10 4  to 10 8  of said cells per kilogram of the subject's mass are used. 
     
     
         46 . A method according to  claim 31 , wherein one or more doses of 10 4  to 10 8  of said cells per kilogram of the subject's mass are used. 
     
     
         47 . A method according to  claim 42 , wherein one or more doses of 10 4  to 10 8  of said cells per kilogram of the subject's mass are used. 
     
     
         48 . A method according to  claim 28 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         49 . A method according to  claim 29 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         50 . A method according to  claim 30 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         51 . A method according to  claim 31 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         52 . A method according to  claim 42 , wherein said cells are in a formulation comprising one or more other pharmaceutically active agents. 
     
     
         53 . A method according to  claim 28  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         54 . A method according to  claim 29  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         55 . A method according to  claim 30  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         56 . A method according to  claim 31  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         57 . A method according to  claim 42  wherein said cells are administered by an intravenous or other parenteral method. 
     
     
         58 . A method according to any of  claims 28  through  56 , wherein said cells are derived from bone marrow.