Therapeutic immune modulation by stem cell secreted exosomes
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.
1. A method of enhancing stem cell engraftment 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 cell population;
d) concentrating said exosomes; and
e) administering said exosomes and said stem cells to said mammal.
2. The method of claim 1 , wherein said stem cells are endometrial regenerative cells (ERC).
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 stern 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 the group consisting of a) ultracentrifugation; b) column chromatography; c) size exclusion; and d) filtration through a device containing an affinity matrix selective towards exosomes.
6. 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.
7. 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.
8. A method of enhancing stem cell engraftment in a mammal comprising
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 cell population;
d) concentrating said exosomes to at least 1 μg/mL; and
e) administering 1-2 μg of said exosomes and at least 100,000 of said stem cells to the mammal.
9. The method of claim 8 , wherein said stem cells are endometrial regenerative cells (ERC).
10. The method of claim 8 , further comprising incorporating one or more autoantigens into said exosomes generated from said stem cells.
11. The method of claim 8 , further comprising transfecting the stem cell population with one or more autoantigens representing said autoimmune condition.
12. A method of treating a cardiac enhancing stem cell engraftment in a human patient in need of therapy comprising:
a) obtaining a mesenchymal stem cell;
b) introducing into said mesenchymal stem cell an antigen, wherein said antigen is present in one or more exosomes released by said mesenchymal stem cell;
c) purifying said exosomes and concentrating said exosomes to at least 1 μg/mL;
d) administering an amount of said exosomes and an amount of said stem cells into the human patient in need of therapy effective to inhibit T cell proliferation.
13. The method of claim 12 , wherein said mesenchymal stem cell is an endometrial regenerative cell (ERC).
14. The method of claim 13 wherein ERC are cultured in a DMEM F12 medium comprising approximately 10% fetal calf serum for a period of 1-100 hours.
15. The method of claim 12 , wherein said exosomes are concentrated by a means selected from: a) ultracentrifugation; b) column chromatography; c) size exclusion; and d) filtration through a device containing an affinity matrix selective towards exosomes.
16. The method of claim 12 , wherein said antigen is incorporated into said exosome-producing mesenchymal stem cell by one or more of a) transfection with the gene encoding said antigen; b) transfection with said antigenic protein; and c) transfection with said antigenic peptide.
17. The method of claim 12 , wherein said antigen is loaded onto said exosomes.
18. The method of claim 17 , wherein said loading is accomplished through chemical means.