Significant reduction in T cell proliferation was observed in case of both P-MSC and C-MSC co-cultures [Fig. T regulatory cells were enriched in case of P-MSCs in both, MSC-MNC and MSC-DC co-cultures. This observation was further supported by increased mRNA expression of FoxP3 in P-MSCs. Presently, Glycerol 3-phosphate cord-derived MSCs are being employed in transplantation therapies parallel to the bone marrow-derived MSCs. Our findings suggest that P-MSCs can be a better alternative to C-MSCs, to provide aid in immunological ailments. Mesenchymal stem cells (MSCs) belong to the category of adult stem cells, Glycerol 3-phosphate of the non-haematopoietic lineage, found to be resident in many tissues, where they act as a pool of self renewing cells which can differentiate into desired cell type after a tissue injury1,2. These cells, isolated and identified first by Friedenstein from bone marrow (BM)3, are best known for their proliferative and mesodermal lineage differentiation ability on the basis of which they are now been used in many tissue repair regimes. Although isolation of MSCs has been successfully achieved from other tissues, such as adipose tissue, gingiva, placenta, umbilical cord, etc.2,4,5, variations in terms of their extent of proliferation and behaviour have been reported. Among all the sources, the umbilical cord tissues have the least ethical constraints being majorly clinical wastes and involve no invasive method for procurement. The beneficial effect of MSCs in alleviating the diseased state is attributed to their cytokine secretion, migration ability and the immunomodulatory function. Their immune regulatory properties have been evaluated in animal models of multiple sclerosis6,7 and rheumatoid arthritis8,9, where the impact is on the cells of immune system. MSCs exert regulatory effects on various cells of immune system such as dendritic cells, NK cells and T cells10,11,12. It is well established that MSCs lack the MHC class II molecule and hence do not mount an immune response; but instead they secrete cytokines such as prostaglandin E2 (PGE2), Interleukin 10 (IL-10), Interleukin 6 (IL-6), transforming growth factor (TGF), hepatocyte growth factor (HGF) etc. that are known to be involved in anti-inflammatory responses13,14,15. The effect of MSCs is seen on the maturation of antigen presenting cells, wherein they downregulate the expression of co-stimulatory molecules, thereby affecting the immunogenic response12,16. These properties have been successfully used in graft versus host disease (GVHD)17,18 in many clinical trials along with other immune-related diseases. However, in all the studies reported, bone marrow-derived MSCs from allogenic sources are used and umbilical cord tissue-derived MSCs are now being introduced19. Studies with bone marrow and umbilical cord derived MSCs have looked into their immunosuppressive properties with a concomitant increase in the regulatory T cell fraction after MSC administration20,21. But a source-dependent variation in the behaviour of MSCs has been observed. Here, we compared the immunomodulatory potential of MSCs derived from placenta and umbilical cord, obtained from the same individual. Very few reports talk about the source dependent analysis of the effect of MSCs on the immune cells, where the comparison of sources is from different donors22. The donor Glycerol 3-phosphate variation in this context cannot be neglected suggesting a need to isolate MSCs from different sources obtained from the same donor23. To study this effect, we co-cultured MSCs derived from human umbilical cord and placenta either with mononuclear cells or with dendritic cells. The HDAC10 effect mounted by this co-culture on the T cells in a mixed leukocyte reaction (MLR) was then assessed. We looked into the enrichment of any specific T cell subset in the MLR due to the presence of MSCs. We went on to examine the regulatory milieu by analyzing the cytokine profile of the MLRs. We report here that P-MSCs bring about higher reduction in T cell proliferation in both types of MLRs compared to C-MSCs, and this is mainly due to the enrichment of regulatory T cell subset. A cell to cell contact is not necessary as even the CMs from the two types of MSCs showed a similar effect. Thus, by using paired samples C to minimize the sample variation and define the condition set of the isolated tissues C we show for the first time conclusively that there are striking differences in the two types of MSCs in their immunomodulatory behaviour. This study will help investigators to identify the proper source for MSCs in treatment of conditions like GVHD. Results Placenta- and umbilical cord-derived MSCs from paired samples showed similar phenotype, but different clonogenic ability The MSCs derived from placenta and umbilical cord displayed typical fibroblastic morphology [Fig. 1a,b]. They also showed a similar marker expression profile, where they showed more than 90% expression for CD73, CD105, CD166,.