Immunological Profile of Adult Human Mesenchymal Stem Cells Derived from Various Sources - Bone Marrow, Adipose Tissue and Umbilical Cord Matrix / Blood

Abstract

Mesenchymal stem cells were successfully isolated, and expanded from both primitive and adult sources. Isolated MSCs were characterized as per the criteria laid down by ISCT. Mesenchymal Stromal Cells (MSCs) are very advantageous in the field of regenerative medicine due to their immunomodulatory properties. However, reports show that these properties vary from source to source. Hence, understanding the source-dependent specificity of MSCs in their immunomodulatory abilities will enable optimal use of MSCs in cell-based therapies. This study investigated the human MSCs from three different sources: adipose tissue (AT), bone marrow (BM) and Wharton s jelly (WJ) with respect to phenotypic responses of human peripheral blood mononuclear immune cells (MNCs) and the concurrent changes in cytokine expressions in MSCs, under a mitogen stimulated co-culture condition. The study employed cytometric analysis for studying the immunoregulatory properties of MSCs and cytokine profiling using a customized PCR array and solid-phase sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The results reveal differential modulation of both immune cells as well as MSCs upon activation by the mitogen PHA, independently and in co-culture. Notably, we observed source-specific MSC-cytokine-signatures under stimulated conditions. The study results show that AT-MSCs up-regulate VEGF, BM-MSCs up-regulate PTGS-2 and WJ-MSCs increase expression of IDO over several fold as compared to the controls. This remarkable increase in source specific cytokine expression was also validated at a functional level by quantitative protein expression studies. In our hands, even though MSCs from AT, BM and WJ sources exhibit characteristic immunomodulatory properties, study results highlight that MSCs sourced from different tissues may exhibit unique cytokine signatures and thus may be suitable for specific regenerative applications. From this study, it is concluded that further pre-clinical and clinical studies can be pursued by using the MSCs derived from the WJ source.