Pharmaceutical composition comprising stem cells treated with NOD2 agonist or culture thereof for prevention and treatment of immune disorders and inflammatory diseases
The present invention relates to a pharmaceutical composition for the prevention or treatment of immune disorders and inflammatory diseases, comprising stem cells that are generated by culturing stem cells expression Nucleotide-binding Oligomerization Domain protein 2 (NOD2) with a NOD2 agonist or a culture thereof. More particularly, the present invention relates to a method for suppressing immune responses or inflammatory responses of a subject, comprising the step of administering the pharmaceutical composition, the stem cells or culture thereof to the subject, a method for preparing an immunosuppressive drug or an anti-inflammatory drug using the stem cells or culture thereof, a method for preparing PGE 2 or TGF-β1 comprising the step of culturing NOD2-expressing stem cells in culture medium with a NOD2 agonist, a graft comprising stem cells expressing NOD2 and the NOD2 agonist, a method for preparing the graft, a composite comprising stem cells expressing NOD2 and the NOD2 agonist, and a culture generated by culturing the NOD2-expressing stem cells with a NOD2 agonist.
1. A method for suppressing immune responses or inflammatory responses of a subject comprising the steps of
(a) determining expression of Nucleotide-binding Oligomerization Domain protein 2 (NOD2) in isolated mesenchymal stem cells;
(b) treating the cells expressing NOD2 with a NOD2 agonist to increase the production of prostaglandin E2 (PGE2) or transforming growth factor beta 1 (TGF-β1) and culturing them; and
(c) providing the cells producing PGE2 or TGF-β1 of step (b) or a culture thereof to the subject.
2. The method according to claim 1 , wherein the method suppresses inflammatory responses of a subject.
3. The method according to claim 1 , wherein the suppression of immune responses inflammatory responses is accomplished by activation NOD2-Rip2 pathway.
4. The method according to claim 1 , wherein the NOD2 agonist is muramyl dipeptide (MDP).
5. The method according to claim 1 , wherein the mesenchymal stem cells or a culture thereof perform as an immunosuppressive drug or an anti-inflammatory drug.
6. The method according to claim 1 , wherein the concentration of the NOD2 agonist in a culture medium is 1 to 100 μg/ml, and incubation time after addition of the NOD2 agonist is 0.1 to 200 hours.
7. The method according to claim 1 , wherein the mesenchymal stem cells secrete prostaglandin E 2 (PGE 2 ) or transforming growth factor beta 1 (TGF-β1) during the culturing, and wherein the culture thereof comprises PGE 2 or TGF-β1.