Therapeutic immune modulation by stem cell secreted exosomes

Abstract

Disclosed are methods, compositions of matter, and protocols useful for the induction of a therapeutic immune modulatory response through administration of exosomes derived from a stem cell source. In one embodiment, said stem cell source is endometrial regenerative cells. Specifically, in one embodiment stem cell derived exosomes are used as a method of treating an autoimmune condition such as rheumatoid arthritis, multiple sclerosis, or systemic lupus erythromatosis.

What is claimed is: 
     
         1 . A method of inducing immune modulation in a mammal comprising the steps of:
 a) extracting a stem cell population; b) culturing said stem cell population for a sufficient time point, under conditions permissible for exosome production; c) collecting exosomes generated by said stem cells; d) concentrating said exosomes; and e) administering said exosomes to said mammal.   
     
     
         2 . The method of  claim 1 , wherein said stem cell comprises a cell selected from: a) a progenitor cell; b) a pluripotent stem cell; c) an induced pluripotent stem cell; d) a hematopoietic stem cell; e) a very small embryonic like stem cell; f) a mesenchymal stem cell; g) an endometrial regenerative cell (ERC); h) a progenitor cell; and i) a monocyte. 
     
     
         3 . The method of  claim 1 , wherein said stem cells are induced to produce an increased amount of exosomes. 
     
     
         4 . The method of  claim 3 , wherein said induction of exosomes from said stem cells is achieved by treatment of said stem cells with cytokines 
     
     
         5 . The method of  claim 1 , wherein said exosomes are concentrated by a means selected from: a) ultracentrifugation; b) column chromatography; c) size exclusion; d) filtration through a device containing an affinity matrix selective towards exosomes. 
     
     
         6 . The method of  claim 1 , wherein said exosomes generated from said stem cells are used to inhibit inflammation in an injured tissue. 
     
     
         7 . The method of  claim 1 , wherein said exosomes are transfected with a genetic material so as to allow delivery of said genetic material to an immune cell. 
     
     
         8 . The method of  claim 1 , wherein said cells producing said exosomes are transferred with a genetic material so as to allow delivery of said genetic material to an immune cell. 
     
     
         9 . A method of treating an autoimmune condition through administration of a population of stem cell exosomes capable of suppressing a biological pathway associated with an immune pathway associated with said autoimmune condition. 
     
     
         10 . The method of  claim 9 , wherein said autoimmune condition is selected from a group comprising of: a) diabetes; b) multiple sclerosis; c) rheumatoid arthritis; d) Hashimoto's thyroiditis; e) graft rejection; and f) graft versus host disease. 
     
     
         11 . A method of treating an autoimmune condition comprising incorporating one or more autoantigens into said exosomes generated from said stem cells, with incorporation of said autoantigen being accomplished by introduction into said stem cell or introduction into said exosome generated by said stem cell and administering said exosomes into a patient in need thereof. 
     
     
         12 . A method of treating an autoimmune condition in a mammal comprising administering exosomes derived from stem cells that have been transfected one or more autoantigens representing said autoimmune condition. 
     
     
         13 . A method of treating an autoimmune condition comprising of: a) obtaining a mesenchymal stem cell; b) introducing into said mesenchymal stem cell an antigen, in a manner such that said antigen is introduced into said mesenchymal stem cell in a manner so that said antigen is incorporated by said mesenchymal stem cell such that said antigen enters the exosomes that are released by said mesenchymal stem cell; c) purifying said antigen bearing exosomes; and d) administering said antigen expressing exosomes into a patient in need of therapy. 
     
     
         14 . The method of  claim 13 , wherein said mesenchymal stem cell is selected from a group of mesenchymal stem cells selected from a group comprising of a) a bone marrow mesenchymal stem cell; b) an adipose derived mesenchymal stem cell; c) a dental pulp derived mesenchymal stem cell; d) a fallopian tube derived mesenchymal stem cell; e) an endometrial regenerative cell (ERC); f) a peripheral blood derived mesenchymal stem cell; g) a cord blood derived mesenchymal stem cell; h) a placental derived mesenchymal stem cell; i) a Wharton's Jelly derived mesenchymal stem cell; k) a menstrual blood derived mesenchymal stem cell; and 1) an endometrial derived mesenchymal stem cell. 
     
     
         15 . The method of  claim 14  wherein ERC are cultured in a DMEM F12 media in approximately 10% fetal calf serum for a period of 1-100 hours. 
     
     
         16 . The method of  claim 13 , wherein said exosomes are concentrated by a means selected from: a) ultracentrifugation; b) column chromatography; c) size exclusion; d) filtration through a device containing an affinity matrix selective towards exosomes. 
     
     
         17 . The method of  claim 13 , wherein said antigen is incorporated into said exosome-producing mesenchymal stem cell through a series of procedures selected from: a) transfection with the gene encoding said antigen; b) transfection with said antigenic protein; and c) transfection with said antigenic peptide. 
     
     
         18 . The method of  claim 13 , wherein said antigen is loaded onto said mesenchymal stem cell produced exosomes. 
     
     
         19 . The method of  claim 18 , wherein said loading of said antigen is accomplished through chemical means.