Method of treating autoimmune disease with mesenchymal stem cells
Methods and compositions for treating an autoimmune disease, such as new onset type 1 diabetes (T1D) in a subject using autologous or allogeneic mesenchymal stem cells administered to the subject prior to autoimmune-induced complete depletion of insulin-producing pancreatic beta cells, e.g., within six months of new onset type 1 diabetes (T1D) diagnosis or prior to the onset of disease in a subject determined to be at high risk for T1D.
1. A method of treating new onset type 1 diabetes (TID) in a subject comprising administering isolated autologous or allogeneic mesenchymal stem cells to the subject within six months of diagnosis of new onset T1D, wherein the isolated autologous or allogeneic mesenchymal stem cells are chosen from isolated autologous or allogeneic mesenchymal stem cells expressing an exogenous programmed death ligand and isolated autologous or allogeneic mesenchymal stem cells overexpressing an endogenous programmed death ligand, and wherein the programmed death ligand is chosen from PD-L1 or PD-L2.
2. The method of claim 1 , wherein the programmed death ligand is PD-L1.
3. The method of claim 1 , wherein the programmed death ligand is PD-L2.
4. A method of treating new onset type 1 diabetes (T1D) in a human subject comprising:
identifying a subject comprising pancreatic islet beta cells and T cells autoreactive against the pancreatic islet beta cells (beta-cell-autoreactive T cells), wherein the subject received a diagnosis of new onset type 1 diabetes (T1D) within the previous six months; and
exerting an immunosuppressive effect on the beta-cell-autoreactive T cells in the subject, wherein:
the exerting of the immunosuppressive effect comprises administering isolated autologous or allogeneic mesenchymal stem cells to the subject within six months of new onset type 1 diabetes (T1D) diagnosis.
5. The method of claim 4 , wherein the mesenchymal stem cells are administered within 24 hours of T1D diagnosis.
6. The method of claim 4 , wherein the exerting of the immunosuppressive effect further comprises a second administration of autologous or allogeneic mesenchymal stem cells within ten days of the first administration of autologous or allogeneic mesenchymal stem cells.
7. The method of claim 4 , wherein the exerting of the immunosuppressive effect further comprises a second administration of autologous or allogeneic mesenchymal stem cells within six months of the first administration of autologous or allogeneic mesenchymal stem cells.
8. The method of claim 4 , wherein the mesenchymal stem cells are derived from bone marrow or peripheral blood.
9. The method of claim 4 , wherein the mesenchymal stem cells are derived from a population of cells selected from the group consisting of umbilical cord blood cells, muscle cells, fat cells, embryonic yolk sac cells, placenta cells, fetal blood cells, fetal skin cells, and adult skin cells.
10. The method of claim 4 , wherein the mesenchymal stem cells are administered to a subject having an abnormally low, but measurable, serum C-peptide level.
11. The method of claim 10 , wherein the subject has a stimulated C-peptide test integrated C-peptide level of 1.0 nmol/L or less.
12. The method of claim 11 , wherein the subject has a measurable increase in stimulated C-peptide test integrated C-peptide level of 0.54 nmol/L or less.
13. The method of claim 4 , wherein the subject has a detectable level of pancreatic autoantibody.
14. The method of claim 4 , wherein the mesenchymal stem cells are allogeneic.
15. The method of claim 4 , further comprising administering to the subject an immunosuppressive agent.
16. The method of claim 15 , wherein the immunosuppressive agent is selected from the group consisting of prednisone, azathioprine, cyclosporine, antibodies against CD3, antibodies against CD20, and antithymocyte globulin.
17. The method of claim 4 , further comprising administering to the subject a peptide vaccine.
18. The method of claim 17 , wherein the vaccine induces tolerance of insulin-producing cells.
19. The method of claim 18 , wherein the vaccine comprises an autoimmune Type I diabetes (T1D) autoantigen.
20. The method of claim 19 , wherein the vaccine comprises an islet-cell autoantigen selected from the group consisting of insulin, proinsulin, glutamic acid decarboxylase (GAD65), HSP60, and IA-2 protein tyrosine phosphatase.
21. The method of claim 4 , further comprising administering a non-mitogenic anti-CD3 active compound selected from the group consisting of CD3 antibodies and fragments of CD3 antibodies.
22. The method of claim 21 , wherein the non-mitogenic anti-CD3 active compound is administered in an injectable form comprising 5 to 20 mg of the non-mitogenic anti-CD3 active compound.