THERAPEUTIC METHODS AND COMPOSITIONS
Disclosed herein are pharmaceutical compositions and methods comprising or utilizing placental adherent stromal cells. The pharmaceutical compositions may be indicated for ameliorating or treating various disorders, e.g., impaired glucose tolerance. Alternatively, the pharmaceutical composition may be indicated for ameliorating or treating systemic inflammation, e.g., in a subject with impaired glucose tolerance. The pharmaceutical compositions may further include pharmacologically acceptable excipients.
1 . A method of ameliorating impaired glucose tolerance in a subject in need thereof, comprising: administering to the subject a pharmaceutical composition, comprising placental adherent stromal cells (ASC), thereby ameliorating impaired glucose tolerance.
2 . The method of claim 1 , wherein said subject is at least 60 years of age at the onset of treatment.
3 . The method of claim 1 , wherein said subject has a HbA1c value of at least 43.5 mmol/mol at the onset of treatment.
4 . The method of claim 1 , wherein said subject has a body mass index of at least 27.5 kg/m 2 at the onset of treatment.
5 . A method of reducing systemic inflammation in a subject with impaired glucose tolerance in a subject in need thereof, comprising: administering to the subject a pharmaceutical composition, comprising placental adherent stromal cells (ASC), thereby reducing systemic inflammation in a subject with impaired glucose tolerance.
6 - 8 . (canceled)
9 . The method of claim 1 , wherein said ASC have been incubated on a 3D culture substrate in a bioreactor.
10 . The method of claim 9 , further comprising the subsequent step of harvesting said ASC by removing said ASC from said 3D culture apparatus.
11 . The method of claim 9 , wherein said ASC have been incubated on a 2D adherent-cell culture substrate, prior to incubation in said 3D culture apparatus.
12 . (canceled)
13 . The method of claim 9 , wherein said 3D culture substrate comprises a synthetic adherent material formed as a fibrous matrix, wherein said synthetic adherent material is selected from the group consisting of a polyester, a polypropylene, a polyalkylene, a polyfluorochloroethylene, a polyvinyl chloride, a polystyrene, a polysulfone, a cellulose acetate, a glass fiber, a ceramic particle, a poly-L-lactic acid, and an inert metal fiber.
14 - 16 . (canceled)
17 . The method of claim 1 , wherein said administering comprises:
a. administering to the subject a first pharmaceutical composition, comprising allogeneic placental ASC from a first donor; and
b. administering to said subject, at least 7 days after step a), a second pharmaceutical composition comprising allogeneic placental ASC from a second donor, wherein said second donor differs from said first donor in at least one allele group of human leukocyte antigen (HLA)-A or human leukocyte antigen (HLA)-B.
18 . The method of claim 17 , further comprising administering to said subject, at least 7 days after step b), a third pharmaceutical composition comprising allogeneic ASC of a third donor, wherein said third donor differs from both said first donor and said second donor in at least one allele group of HLA-A or HL A-B.
19 . The method of claim 1 , wherein said ASC express a marker selected from the group consisting of CD73, CD90, CD29 and CD105.
20 . The method of claim 19 , wherein said ASC do not express a marker selected from the group consisting of CD3, CD4, CD11b, CD14, CD19, and CD34.
21 . The method of claim 19 , wherein said ASC do not express a marker selected from the group consisting of CD3, CD4, CD34, CD39, and CD106.
22 . (canceled)
23 . The method of claim 21 , wherein more than 50% of said ASC express CD200.
24 . The method of claim 21 , wherein more than 50% of said ASC express CD141.
25 . The method of claim 21 , wherein more than 50% of said ASC express SSEA4.
26 . The method of claim 25 , wherein said ASC secrete Flt-3 ligand or stem cell factor (SCF).
27 . The method of claim 1 , wherein the cells are administered intramuscularly.
28 . The method of claim 1 , wherein the cells are administered intravenously, subcutaneously, or intraperitoneally.