Problem We have previously shown that stroma of human palatine tonsils contains mesenchymal stem cells (MSCs) that can be isolated and expanded in culture. These tonsil-derived MSCs (T-MSCs) show multipotent differentiation properties, i.e. can differentiate along multiple mesenchymal lineages, including osteoblasts, chondrocytes, adipocytes, and myocytes. Recent findings also show that MSCs display immunoregulatory properties. Although the exact immunosuppressive mechanisms are unknown, the capacity of MSCs to suppress T-cell proliferation stimulated by allogeneic lymphocytes, dendritic cells, and phytohemaglutinin (PHA) is well documented. This study explores immunosuppressive characteristics of T-MSCs and compares them with characteristics of bone marrow-derived MSCs (BM-MSCs), a well-characterized cell population. Methods The mixed lymphocyte reaction (MLR) using human peripheral blood mononuclear cells (PBMC) from healthy donors and xenogeneic murine splenocytes was used to test the immunosuppressive properties of T-MSCs and BMMSCs. Indoleamine 2,3-dioxygenase (IDO) enzyme activity was measured spectrophotometrically based on tryptophan-to-kynurenine conversion in the supernatant. Interferon (IFN)-g in culture supernatants was quantified using a commercially available ELISA kit. Results Addition of BM-MSCs and T-MSCs both inhibited the PHA-induced proliferative response of PBMC and xenogeneic splenocytes. The difference in immunosuppressive activity correlates with the level of cell surface interferon (IFN)-g receptor as well as the differential ability of IFN-g to stimulate of IDO activity by T-MSCs compared to BM-MSCs. Conclusion T-MSCs share similar immunosuppressive characteristics as BM-MSCs in MLR. The immunosuppressive activity is significant and dose-dependent, although at a lower level than that of BM-MSCs. Significance Owing to their ease of isolation, rapid proliferation in the culture and self-renewal capacity, MSCs to date are considered an attractive candidate cell type for the development of novel cell-based therapies. They could be relevant in a wide range of clinical applications, including tissue and organ repair, drug or gene delivery to diseased tissues, improvement of allogenic hematopoietic cell transplantation, and the management of graft-versus-host disease. Support Supported by NIAMS Intramural Research Program (NIH ZO1 AR 41131). Sasa Janjanin is a recipient of the Fulbright Scholarship of the U.S. Department of State.
Repair cell first, then regenerate the tissues and organs
