TREATMENT OF RHEUMATOID ARTHRITIS USING PLACENTAL STEM CELLS
Provided herein are methods of treatment of individuals having an immune-related disease, disorder or condition, for example, inflammatory bowel disease, graft-versus-host disease, multiple sclerosis, rheumatoid arthritis, psoriasis, lupus erythematosus, diabetes, mycosis fungoides (Alibert-Bazin syndrome), or scleroderma using placental stem cells or umbilical cord stem cells.
1 .- 18 . (canceled)
19 . A method of treating an individual having or at risk of developing rheumatoid arthritis, comprising administering to the individual a therapeutically effective amount of placental stem cells or umbilical cord stem cells, or culture medium conditioned by placental stem cells or umbilical cord stem cells, wherein the therapeutically effective amount is an amount sufficient to cause a detectable improvement in one or more symptoms of said rheumatoid arthritis, or a condition adjunct to said rheumatoid arthritis; wherein said placental stem cells or umbilical cord stem cells:
are CD34−, CD10+, CD105+, and CD200+;
are CD200+ and HLA-G+;
are CD73+, CD105+, and CD200+;
are CD200+ and OCT-4+; or
are CD73+, CD105+ and HLA-G+.
20 . The method of claim 19 , wherein said placental stem cells are CD34−, CD10+, CD105+, and CD200+.
21 . The method of claim 19 , wherein said placental stem cells are CD73+, CD105+, and CD200+.
22 . The method of claim 21 , wherein said placental stem cells are additionally CD34−, CD38− and CD45−.
23 . The method of claim 22 , wherein said placental stem cells are additionally HLA-G+.
24 . The method of claim 19 , wherein said placental stem cells or umbilical cord stem cells are CD200+ and OCT-4+.
25 . The method of claim 24 , wherein said placental stem cells or umbilical cord stem cells are additionally CD73+ and CD 105+.
26 . The method of claim 25 , wherein said placental stem cells are additionally CD34−, CD38− and CD45−.
27 . The method of claim 19 , wherein said one or more symptoms comprises morning stiffness of over an hour in duration, soft-tissue swelling of one or more joints or joint groups, joint pain, subcutaneous nodules, rheumatoid factor present at above 95th percentile, or radiological changes indicating joint erosion.
28 . The method of claim 19 , wherein said condition adjunct to rheumatoid arthritis is pyoderma gangrenosum, neutrophilic dermatosis, Sweet's syndrome, viral infection, erythema nodosum, lobular panniculitis, atrophy of digital skin, palmar erythema, diffuse thinning (rice paper skin), skin fragility, subcutaneous nodules on an exterior surface, e.g., on the elbows, fibrosis of the lungs (e.g., as a consequence of methotrexate therapy), Caplan's nodules, vasculitic disorders, nail fold infarcts, neuropathy, nephropathy, amyloidosis, muscular pseudohypertrophy, endoscarditis, left ventricular failure, valulitis, scleromalacia, mononeuritis multiplex, or atlanto-axial subluxation.
29 . The method of claim 19 , comprising additionally administering at least one therapeutic agent in addition to said placental stem cells.
30 . The method of claim 29 , wherein said therapeutic agent is a glucocorticoid, a non-steroidal anti-inflammatory drug, acetaminophen, ibuprofen, aspirin, an opiate, or topical lidocaine, azathioprine, cyclosporine A, D-pennicillamine, gold salts, hydroxychloroquine, leflunomide, methotrexate, minocycline or sulfasalazine, etanercept, infliximab, adalimumab, rituximab, or abatacept.
31 . The method of claim 19 , wherein a plurality of said placental stem cells or umbilical cord stem cells have been genetically engineered to express IL-1Ra (interleukin-1 receptor antagonist).
32 . The method of claim 31 , wherein said IL-1Ra is a fusion protein comprising IL-1Ra and DHFR (dihydrofolate reductase)
33 . The method of claim 32 , wherein said placental stem cells or umbilical cord stem cells have been transformed with a nucleic acid encoding IL-1Ra-DHFR fusion protein, wherein expression of the fusion protein is enhanced by an methotrexate.
34 . The method of claim 33 , wherein said the nucleic acid encodes IL-1Ra-DHFR-IRES-Luc, where IRES is an internal ribosomal entry site, and Luc is luciferase.