Enhanced MSC preparation

Patent metadata

Field	Value
Publication number	US-10550369-B2
Application number	US-201815945148-A
Country	US
Kind code	B2
Filing date	Apr 4, 2018
Priority date	Oct 8, 2010
Publication date	Feb 4, 2020
Grant date	Feb 4, 2020

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Mesoblast Int Sarl

Inventors

• Tom Samson
• Ton Christopher
• Danilkovitch Alla

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title