Biology session

Bone marrow-derived stromal or mesenchymal stem cells (BMSCs) have recently been in the center of attention due to their ability to support hematopoiesis, tissue maintenance and regeneration, and to their immunosuppressive characteristics. There are several reports focusing on the use of these cells as potential immunosuppressants in the treatment of autoimmune diseases, such as acute graft versus host disease or Chron-disease. Further studies showed that not only BMSCs but MSCs from other tissues are also capable of performing immunosuppression with altering rate. Our aim was to prove and investigate the role and effectiveness of adipose-derived stem cells (ASCs) in immunosuppressive processes compared with MSCs of bone marrow (BM) origin knowing the importance of finding a more easier accessible source of immunosuppressive cells, since usable BM is in limited availability while adipose tissue is easily accessible in great amounts. In our studies we used 10-12 weeks old mice to grow MSC cultures obtained from their BM and visceral fat. These adherent cells were tested for rate of proliferation, multilineage differentiation capacity and immunomodulatory activity. Cells were found to be identical in rate of proliferation and differentiation towards adipocyte and osteoblast lineages. Both type of cells expressed MSC surface markers and were negative for hematopoietic markers. Mitogen (ConA) and also alloantigen induced T-cell proliferation were successfully inhibited in the presence of both BMSCs and ASCs, although ASCs proved to be slightly less effective than BMSCs in identical MSC-concentrations, however, this effect still remains significant. We need to do more research to understand the causes behind the difference in ASC- and BMSC-effectiveness and the mechanism of immunosuppression including certain soluble mediators involved in inflammatory and immune-processes, such as prostaglandin E-2 (PGE-2), tumor necrosis factor alpha-induced protein 6, and indoleamine 2,3-dioxygenase enzyme. First, the production of PGE-2 by MSCs is being tested in this work. We found that BM-derived, as well as adipose tissue derived MSCs, constitutively secreted low amount of PGE-2. Activated T lymphocytes, secreting high amount of interferon-gamma, have significantly upregulated MSC production of PGE-2. Moreover, addition of indomethacin, a specific cyclooxygenase-2 inhibitor markedly reduced PGE-2 secretion by MSCs. In parallel, MSCs lost most, but not all, of their immunsuppressive activity in vitro. These data suggest, therefore, that PGE-2 has an important role in regulating adipose tissue derived MSC immunomodulatory activity, as already described for MSCs isolated from the BM. According to our results so far, ASCs could be used in immune-therapy, however, further in vivo studies are needed to test whether the experienced slight difference in immunosuppressive activity affects the effectiveness and therefore the usability of these cells.