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 treating an inflammatory disease in a subject, the method comprising administering to the subject a composition comprising genetically unmodified stem cells wherein said genetically unmodified stem cells 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 said genetically unmodified stem cells express Ang1 in an amount between 0.1 μg/10 6 cells and 1.0 μg/10 6 cells.
3. The method of claim 1 , wherein said genetically unmodified stem cells express vascular endothelial growth factor (VEGF) in an amount less than about 0.0 3 μg/10 6 cells.
4. The method of claim 1 , wherein said genetically unmodified stem cells express Ang1:VEGF at a ratio between 5:1 and 20:1.
5. The method of claim 1 , wherein said genetically unmodified stem cells are mesenchymal lineage precursor cells.
6. The method of claim 1 , wherein said stem cells are mesenchymal stem cells.
7. The method of claim 1 , wherein the inflammatory disease is diabetes or an associated condition or symptom of diabetes.
8. The method of claim 7 , wherein any one of the following indicates that the diabetes or associated condition or symptom of diabetes has been treated in the subject:
reduction in HbA1c value (% of total haemoglobin);
reduction in fasting insulin levels;
reduction in IL-6 levels;
reduction in TNF-α levels; and/or
increase in adiponectin levels.
9. The method of claim 7 , wherein the subjects glucose levels are inadequately controlled by metformin.
10. The method of claim 7 , wherein the subject has a baseline HbA1c value greater than 7.5%.
11. The method of claim 7 , wherein the associated condition or symptom of diabetes is selected from the group consisting of abnormal wound healing, symptoms of a heart attack, symptoms of a stroke, symptoms of peripheral vascular disease, amputation, symptoms of kidney disease, kidney failure, blindness, neuropathy, nephropathy, retinopathy, inflammation, impotence or nonalcoholic steatohepatitis (NASH).
12. The method of claim 1 , wherein the inflammatory disease is type II diabetes.
13. The method of claim 1 , wherein the method comprises administering about 0.1×10 6 to about 3×10 6 stem cells per kg to the subject.
14. The method of claim 1 , wherein the inflammatory disease is rheumatoid arthritis.
15. The method of claim 14 , wherein any one of the following indicates that the rheumatoid arthritis has been treated:
ACR20;
ACR50;
ACR70;
reduction in IL-6 levels; and/or
reduction in disease activity score.
16. The method of claim 1 , wherein the inflammatory disease is diabetic nephropathy.
17. The method of claim 16 , wherein any one of the following indicates that the diabetic nephropathy has been treated:
inhibition of decline in eGFR and/or mGFR;
improvement in eGFR and/or mGFR; and/or
reduction in IL-6 levels.
18. The method of claim 16 , wherein the subjects baseline eGFR is greater than about 35 ml/min/1.73 m 2 .
19. The method of claim 16 , wherein the subjects baseline eGFR is greater than 25 ml/min/1.73 m 2 .
20. The method of claim 1 , wherein said stem cells are administered systemically or intravenously.