Treatment of immune disorders
View Patent ↗The present disclosure relates to stem cells which express high levels of Angeopoetin-1 (Ang1) and uses thereof in inhibiting M1-type macrophage production and treating inflammatory disease such as diabetes.
1. A method of increasing production and/or function of anti-inflammatory cells in a subject in need thereof, the method comprising administering to the subject a composition comprising genetically unmodified stem cells wherein said genetically unmodified stem cells are mesenchymal precursor cells and express angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) at a ratio [Ang1:VEGF] between 2:1 and 30:1.
2. The method of claim 1 , wherein the anti-inflammatory cells are Th2 cells, TReg cells or M2-type macrophages.
3. The method of claim 2 , wherein the M2-type macrophages are CD14++CD16+.
4. The method of claim 1 , wherein the method increases the number of M2-type macrophages in the subject.
5. The method of claim 1 , wherein the method increases the number of M2-type macrophages to at least 10% of the total monocyte population in the subject.
6. The method of claim 1 , wherein the method increases the number of M2-type macrophages to at least 80% of the total monocyte population in the subject.
7. The method of claim 1 , wherein the method promotes the polarization of macrophages from an M1 to an M2 phenotype.
8. The method of claim 1 , wherein the method promotes the differentiation of pro-inflammatory T helper cells to Th2 or TReg cells.
9. The method of claim 8 wherein the pro-inflammatory T helper cells are Th17 cells.
10. The method of claim 1 , wherein the increased production and/or function of anti-inflammatory cells in the subject results in:
a reduction in IL-6 level in the subject;
a reduction in TNF-alpha level in the subject; and/or,
an increase in IL-10 level in the subject.
11. The method of claim 1 , wherein the method increases the level of IL-10 in the subject and/or decreases the levels of any one of IL-6, TNF-alpha and/or IL-17 in the subject.
12. The method of claim 1 , wherein the method also inhibits the production and/or function of pro-inflammatory cells.
13. The method of claim 12 , wherein the pro-inflammatory cells are Th17 cells or M1-type macrophages.
14. The method of claim 1 , wherein said genetically unmodified stem cells express vascular endothelial growth factor (VEGF) in an amount less than 0.05 μg/10 6 cells.
15. The method of claim 1 , wherein said genetically unmodified stem cells express Ang1:VEGF at a ratio of at least 20:1.
16. The method of claim 1 , wherein the method comprises administering 0.1×10 6 to 3×10 6 stem cells per kg to the subject.
17. The method of claim 1 , wherein said genetically unmodified stem cells express Ang1:VEGF at a ratio between 5:1 and 20:1.
18. The method of claim 1 , wherein said genetically unmodified stem cells express Ang1 in an amount between 0.1 μg/10 6 cells and 1.0 μg/10 6 cells.
19. The method of claim 1 , wherein said genetically unmodified stem cells express Vascular Endothelial Growth Factor (VEGF) in an amount less than 0.03 μg/10 6 cells.