Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord-derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)-DR and co-stimulatory molecules CD80 and CD86 that are required for T-cell activation. More importantly, UCMSCs constitutively express a negative regulator of T-cell activation, B7-H1, and its expression is increased after interferon-c (IFN-c) treatment. In addition, IFN-c treatment induced indoleamine 2,3-dioxygenase (IDO) and HLA-DR expression in UCMSCs. Neither control nor IFN-c-treated UCMSCs stimulated allogeneic T-cell proliferation, and both cell populations inhibited third-party dendritic cell (DC)-mediated allostimulatory activity. Addition of a B7-H1-specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1-MT) abrogated the T-cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte-derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell-to-cell contact, although some inhibitory activity was observed with cell-free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy.

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Non-invasive methods for the assessment of distribution, homing, and retention of stem cells are desired for the successful demonstration of stem cell therapy. Cells labeled with (99m)Tc, (18)F, and (111)In have been reported for tracking the cells in vivo. However, they can be tracked only for a limited time due to the short half lives of these isotopes. In this context, stem cells labeled with (51)Cr would be appropriate for tracking cells for a longer period of time owing to their half life of 27.7 days. Here, we have isolated mesenchymal stem cells (MSCs) from umbilical cord tissue, characterized them, and attempted to radiolabel them with (51)Cr for mapping the fate of transplanted MSC cells after an intravenous injection via the tail vein in small animals.

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Background and Objectives: The field of Umbilical cord blood (UCB) hematopoietic stem cell transplantation has had an amazing run since 1988. UCB is being increasing used in related and unrelated transplant settings. A major hurdle, however, in the use of UCB is its low cell dose, which is largely responsible for an elevated risk of graft failure and significantly delayed neutrophils and platelet engraftment. Strategies to increase CD34 ＋ HSC/HPC dose are under development as a direct correlation has been shown between these counts and time for engraftment. One strategy includes the ex vivo expansion of UCB derived CD34 ＋ cells. Methods and Results:We show that the umbilical cord derived mesenchymal stem cells (UCMSCs) can be used as supporting cells for ex vivo expansion of CD34 ＋ cells using low concentrations of cytokine cocktail. The UCMSCs release the cytokines required for maintenance and proliferation of CD34 ＋ cells in the ex vivo culture conditions.More than 25 fold increase in total nucleated cell count (TNC) and more than 20 fold increase in CD34 ＋ cell count has been obtained using this co-culture system. Conclusions: UCMSCs from both, autologous and allogeneic origin can be used for expansion of UCB derived CD34 ＋ cells. The ease of availability and immunoprivileged nature of UCMSCs further holds promise in their use in an allogeneic transplant setting.