Enhanced MSC preparation
The present invention provides preparations of MSCs with important therapeutic potential. The MSC cells are non-primary cells with an antigen profile comprising less than about 1.25% CD45+ cells (or less than about 0.75% CD45+), at least about 95% CD105+ cells, and at least 95% CD166+ cells. Optionally, MSCs of the present preparations are isogenic and can be expanded ex vivo and cryopreserved and thawed, yet maintain a stable and uniform phenotype. Methods are taught here of expanding these MSCs to produce a clinical scale therapeutic preparations and medical uses thereof.
1. A method of treating graft-versus-host-disease (GVHD) in a human in need thereof comprising administering a therapeutic amount of culture-expanded mesenchymal stem cells (MSCs) comprising (i) less than 0.75% CD45+ cells, (ii) at least 95% CD105+ cells, and (iii) at least 95% CD166+ cells, wherein the MSC are capable of inhibiting IL2Rα expression by CD3/CD28-activated peripheral blood mononuclear cells PBMCs by at least 30% relative to a control.
2. The method of claim 1 , wherein the GVHD is steroid-refractory.
3. The method of claim 1 , wherein the MSC were cultured-expanded from cryopreserved MSC.
4. The method of claim 1 , wherein the MSCs express at least 13 pg TNFR1 per million MSCs.
5. The method of claim 1 , wherein the MSC express about 13 pg to about 44 pg TNFRI per million MSCs.
6. The method of claim 1 , wherein said culture-expansion comprises at least 20 population doublings.
7. The method of claim 1 , wherein said culture-expansion comprises at least 30 population doublings.
8. The method of claim 1 , wherein the MSC are autologous.
9. The method of claim 1 , wherein the MSC are allogeneic.
10. The method of claim 1 , wherein the MSC are administered at a dose of 2×10 6 cells/kg.
11. The method of claim 10 , wherein the MSC are administered biweekly.
12. The method of claim 11 , further comprising subsequent weekly infusions.
13. The method of claim 1 , wherein the MSC are obtained from cord blood.
14. The method of claim 1 , wherein the GVHD is grade II GVHD.
15. The method of claim 1 , wherein the GVHD is grade III or grade IV GVHD.
16. A method of treating an autoimmune disease in a human in need thereof comprising administering a therapeutic amount of culture-expanded mesenchymal stem cells (MSCs) comprising (i) less than 0.75% CD45+ cells, (ii) at least 95% CD105+ cells, and (iii) at least 95% CD166+ cells, wherein the MSC are capable of inhibiting IL2Rα expression by CD3/CD28-activated PBMCs by at least 30% relative to a control.
17. The method of claim 16 , wherein the autoimmune disease is inflammatory bowel disease (IBD).
18. The method of claim 17 , wherein the IBD is Crohn's disease.
19. The method of claim 16 , wherein the autoimmune disease is multiple sclerosis, Type 1 diabetes, rheumatoid arthritis, uveitis, autoimmune thyroid disease, scleroderma, Graves' Disease, lupus, autoimmune lymphoproliferative disease (ALPS), demyelinating disease, autoimmune encephalomyelitis, autoimmune gastritis (AIG), or autoimmune glomerular disease.
20. A method of treating asthma in a human in need thereof comprising administering a therapeutic amount of culture-expanded mesenchymal stem cells (MSCs) comprising (i) less than 0.75% CD45+ cells, (ii) at least 95% CD105+ cells, and (iii) at least 95% CD166+ cells, wherein the MSC are capable of inhibiting IL2Rα expression by CD3/CD28-activated PBMCs by at least 30% relative to a control.