IMMUNOMODULATING MESENCHYMAL STEM CELLS
The current invention concerns an isolated mesenchymal stem cell wherein said cell is measuredpositive for mesenchymal markers CD29, CD44 and CD90; and negative for MHC class II molecules,whereinsaid cell secretes immunomodulatory prostaglandin E2 cytokine when present in an inflammatory environment or condition. The current invention also concerns a cell composition comprising said cells and the use thereof in the treatment of immune-related diseases and inflammatory conditions.
1 . An isolated mesenchymal stem cell wherein said cell is measured
a. positive for mesenchymal markers CD29, CD44 and CD90; and
b. negative for MEW class II molecules,
characterized in that said cell secretes immunomodulatory prostaglandin E2 cytokine when present in an inflammatory environment or condition.
2 . Mesenchymal stem cell according to claim 1 , characterized in that said cell has an increased secretion of at least one of the molecules chosen of IL-6, IL-10, TGF-β, NO, or a combination thereof, and a decreased secretion of IL-1 when present in an inflammatory environment or condition.
3 . Mesenchymal stem cell according to claim 1 , characterized in that said cell has a suspension diameter between 10 μm and 100 μm.
4 . Mesenchymal stem cell according to claim 1 , characterized in that said cell has a spindle-shaped morphology.
5 . Mesenchymal stem cell according to claim 1 , characterized in that said cell induces the secretion of PgE2, IL-6, IL-10, NO, or a combination thereof in peripheral blood mononuclear cells and/or inhibits the secretion of TNF-α, IFN-γ, IL-1, or a combination thereof in PBMSCs.
6 . Mesenchymal stem cell according to claim 1 , characterized in that said cell is isolated from blood, preferably peripheral blood.
7 . A cell composition comprising at least 60% of the isolated MSCs according to claim 1 , wherein at least 95% of said cells are single cells.
8 . Cell composition according to claim 7 , characterized in that said isolated MSCs express PgE2, IL-6, IL-10, TGF-β, NO or a combination thereof when in the presence of PBMCs.
9 . Cell composition according to claim 7 , characterized in that said MSCs induce the expression of PgE2, IL-6, IL-10, NO, or a combination thereof in PBMCs and/or inhibit the secretion of TNF-α, IFN-γ, IL-1, or a combination thereof in PBMCs when in the presence of PBMCs.
10 . Cell composition according to any of claim 8 , characterized in that said MSCs and PBMCs are present in a ratio of between 1:0.001 and 1:1000.
11 . Cell composition according to claim 9 , characterized in that said composition when in the presence of PBMCs expresses PgE2 at a concentration of between 10 3 to 10 6 picogram per ml.
12 . Cell composition according to claim 7 for use in the treatment of immune-related diseases and/or inflammatory processes in a subject, preferably a mammalian subject.
13 . Cell composition for use of claim 12 , characterized in that per treatment 10 5 to 10 7 of said isolated MSCs are administered, wherein said administration is preferably by means of intravenous, intraarticular, intramuscular, intralesional, intraarterial, topical, subconjunctival injection or regional perfusion.
14 . Cell composition for use of claim 12 , characterized in that the immune-related illnesses are selected from the group consisting of auto-immune disease, atopic dermatitis, allergies, rheumatoid arthritis, and arthritis; and wherein the inflammatory processes are selected from the group consisting of degenerative joint disease, osteoarthritis, fever, lung asthma, and tendinitis.