Results showed that UCX cells have the capacity terminal chondrogenic differentiation Nutlin-3a Sigma are consistently larger, more regularly shaped, and strongly stain positive for alcian blue. UCX cells have the capacity to suppress T cell proliferation and to induce treg conversion Whartons jelly derived MSCs have been shown to be able to be safely used in allogeneic applications due to both their lack of immunogenicity when Inhibitors,Modulators,Libraries compared to other MSCs, and their marked capacity for localized immuno suppression. In order to evaluate the capacity of UCX cells to modulate T cell activation, peripheral blood mono nuclear cells from 2 different donors were stimu lated with anti CD3, anti CD28 and IL 2 while co cultured with irradiated UCX cells, bone marrow derived mesen chymal stem cells and tumor cells belonging to an acute lymphoblastic leukemia adult cell line as non MSC control.

Results showed that in two different donors, both MSC type cells have an immunosuppressive for tri lineage differentiation into adipocytes, chondro cytes and osteoblasts. Inhibitors,Modulators,Libraries Control samples on the left column are cell cultures undergoing Inhibitors,Modulators,Libraries same cul ture conditions and specific staining reactions but with out addition of differentiation factors. For chondrogenic differentiation, the natural tendency for UCX cells to form three dimensional aggregates has become notice able, even without the addition of differentiaion factors. In any case, chondrospheres resulting from effect when compared to Molt 4. Moreover, UCX cells were able to inhibit T cell proliferation more significantly than BM MSCs, suggesting that these cells are more immunosuppressive than BM MSCs.

The capacity of UCX cells to take a multi modal approach to immune regulation, through induction of Tregs was also evaluated. Tregs are a sub set of naive CD4 CD25 T cells Inhibitors,Modulators,Libraries that express the Foxp3 transcription factor and become regulatory in the periphery in response to a variety of signals, including antigen exposure in the presence of immunosuppressive cytokines Inhibitors,Modulators,Libraries such as TGF B. Previous studies have demonstrated that not all CD4 CD25 cells concomitantly TNF-�� inhibitor expressed Foxp3, while only very few Foxp3 cells resided in the CD25 popula tion. However, Foxp3 remains the best marker to identify regulatory T cell populations. Therefore, in this study we assessed Foxp3 expression in FACS sorted CD4 T cells as indication of Treg conversion. In order to address the putative effect of UCX cells in inducing the conversion of Treg cells we used an in vitro co culture system where sorted polyclonal popu lations of CD4 CD25 T cells from human donors were activated in the presence or absence of UCX cells. It has been shown that immunosuppressive reagents can induce Treg cells independently of the addition of exogenous TGF B to the cultures.