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.

What is claimed is: 
     
         1 . A method of adjunctive treatment of a subject, comprising: administering to a subject at risk for or suffering from an immune dysfunction, by an effective route and in an effective amount to treat the immune dysfunction, cells that: are not embryonic stem cells, embryonic germ cells, or germ cells; can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages; do not provoke a deleterious immune response in the subject; and are effective to treat the immune dysfunction in the subject, wherein the cells are administered adjunctively to one or more other treatments administered to the subject to treat the same thing, to treat something different, or both. 
     
     
         2 . A method according to  claim 1 , wherein said cells can differentiate into at least one cell type of each of the endodermal, ectodermal, and mesodermal embryonic lineages. 
     
     
         3 . A method according to  claim 1 , wherein said cells express telomerase. 
     
     
         4 . A method according to  claim 1 , wherein said cells are positive for oct-3/4. 
     
     
         5 . A method according to  claim 1 , wherein said cells have undergone at least 10 to 40 cell doublings in culture prior to their administration to the subject. 
     
     
         6 . A method according to  claim 1 , wherein said cells are allogeneic to the subject. 
     
     
         7 . A method according to  claim 1 , wherein said cells are administered to the subject adjunctively to another treatment that is administered before, at the same time as, or after said cells are administered. 
     
     
         8 . A method according to  claim 1 , wherein said cells are mammalian cells. 
     
     
         9 . A method according to  claim 8 , wherein said cells are human cells. 
     
     
         10 . A method according to  claim 8 , wherein said cells are derived from cells isolated from placental tissue, umbilical cord tissue, umbilical cord blood, bone marrow, blood, spleen tissue, thymus tissue, spinal cord tissue, or liver tissue. 
     
     
         11 . A method according to  claim 1 , wherein the subject is a mammal. 
     
     
         12 . A method according to  claim 9 , wherein the subject is human. 
     
     
         13 . A method according to  claim 12 , wherein said cells are administered to the subject in one or more doses comprising 10 4  to 10 8  of said cells per kilogram of the subject's mass. 
     
     
         14 . A method according to  claim 12 , wherein the subject will receive or has received a transplant and will be at risk for or has developed a host versus graft response or graft versus host disease, and said cells are administered adjunctively to the transplant. 
     
     
         15 . A method according to  claim 14 , wherein the transplant is an organ transplant, the subject is at risk for or has developed a host versus graft response, and said cells are administered adjunctively to the transplant to treat the host versus graft response. 
     
     
         16 . A method according to  claim 14 , wherein the subject is or will be treated by radiation or chemotherapy or a combination of radiation and chemotherapy, weakening the subject's immune system, and treatment with said cells is adjunctive to the radiation, the chemotherapy, or the combination of the two. 
     
     
         17 . A method according to  claim 14 , wherein said cells are administered to a subject having a compromised immune system. 
     
     
         18 . A method according to  claim 17 , wherein the transplant is a bone marrow or blood transplant, the subject is at risk for or has developed graft versus host disease, and said cells are administered adjunctively to the transplant to treat the graft versus host disease. 
     
     
         19 . A method according to  claim 15 , wherein the subject will be or is being treated with an immunosuppressive agent, and said treatment with said cells is adjunctive thereto. 
     
     
         20 . A method according to  claim 18  wherein the subject will be or is being treated with an immunosuppressive agent, and said treatment with said cells is adjunctive thereto. 
     
     
         21 . A method according to  claim 1 , wherein the subject is at risk for or is suffering from one or more of a neoplasm, an anemia or other blood disorder, and an immune dysfunction, wherein treatment with said cells is adjunctive to a treatment thereof. 
     
     
         22 . A method according to  claim 1 , wherein the subject is at risk for or is suffering from one or more of a myeloproliferative disorder, a myelodysplastic syndrome, leukemia, multiple myeloma, a lymphoma, a hemoglobinopathy, a thalassemia, a bone marrow failure syndrome, sickle cell anemia, aplastic anemia, Fanconi's anemia, an immune hemolytic anemia, a congenital immune deficiency, or an autoimmune dysfunction, wherein treatment with said cells is adjunctive to a treatment thereof.