THERAPEUTIC DOSAGE REGIMENS COMPRISING ADHERENT STROMAL CELLS
Disclosed herein are pharmaceutical compositions and therapeutic dosage regimens comprising or utilizing adherent stromal cells. The adherent stromal cells may be derived e.g. from placental tissue, from adipose tissue, or from bone marrow. The pharmaceutical compositions may be indicated for treating various disorders, e.g. ischemic disorders, hematopoietic disorders, and neurodegenerative disorders, inflammatory disorders, and neoplasms. The pharmaceutical compositions may further include pharmacologically acceptable excipients.
1 . A therapeutic method, comprising:
a. administering to a subject a first pharmaceutical composition, comprising allogeneic adherent stromal cells (ASC) from a first donor; and
b. administering to said subject, at least 7 days after step a), a second pharmaceutical composition comprising allogeneic 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.
2 . The therapeutic method of claim 1 , wherein said second donor differs from said first donor in at least one allele group of HLA-A.
3 . The therapeutic method of claim 1 , wherein said second donor differs from said first donor in at least one allele group of HLA-B.
4 . The therapeutic method of claim 1 , wherein said second donor differs from said first donor in both allele groups of HLA-A or HLA-B.
5 . The therapeutic method of claim 1 , wherein said second donor differs from said first donor in at least one allele supertype of HLA-A or HLA-B.
6 . The therapeutic method of claim 1 , wherein said second donor differs from said first donor in both allele supertypes of HLA-A.
7 . The therapeutic method of claim 1 , wherein step b) is performed between 2-52 weeks after step a).
8 . (canceled)
9 . The therapeutic method of claim 1 , wherein step b) is performed between 6-20 weeks after step a).
10 . The therapeutic method of claim 1 , 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 HLA-B.
11 - 21 . (canceled)
22 . The method of claim 1 , wherein said ASC originate from placenta tissue.
23 . The method of claim 22 , wherein said ASC express a marker selected from the group consisting of CD73, CD90, CD29 and CD105.
24 . The method of claim 22 , wherein said ASC do not express a marker selected from the group consisting of CD3, CD4, CD11b, CD14, CD19, and CD34.
25 . The method of claim 22 , wherein said ASC do not express a marker selected from the group consisting of CD3, CD4, CD34, CD39, and CD106.
26 . The method of claim 25 , wherein less than 50% of said ASC express CD200.
27 . The method of claim 25 , wherein more than 50% of said ASC express CD200.
28 . The method of claim 25 , wherein more than 50% of said ASC express CD141 or SSEA4.
29 . The method of claim 25 , wherein more than 50% of said ASC express HLA-A2.
30 . The method of claim 1 , wherein said ASC originate from adipose tissue or bone marrow.
31 . The method of claim 1 , wherein the cells are administered intramuscularly.
32 . The method of claim 1 , wherein the cells are administered intravenously, subcutaneously, or intraperitoneally.