Differential immunomodulation of human mesenchymal stromal cells from various sources in an inflammation mimetic milieu

• Published in: Cytotherapy (Oxford, England) England), 2022-02, Vol.24 (2), p.110-123
• Main Authors: Meenakshi Sundaram, Rajasundari, Kadapakkam Nandabalan, Sangeetha, Rupert, Secunda, Srinivasan, Prasanna, Sankar, Pavithra, Patra, Bamadeb, Verma, Rama Shankar, Vennila, Rosy, Sathyanesan, Jeswanth, Rajagopal, Surendran
• Format: Article
• Language: English
• Subjects: Adipose tissue; Bone marrow; Bone Marrow Cells; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytokines; Humans; IDO; Immunomodulation; Inflammation; Leukocytes, Mononuclear; Mesenchymal Stem Cells; Mesenchymal stromal cells; PTGS-2; T cell activation; T regulatory cells; VEGF; Wharton Jelly; Wharton's jelly
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2021.09.005

●There are unique differences in the immunomodulatory properties of MSCs sourced from primitive and adult sources upon crosstalk with MNCs.●MSCs suppress the proliferation of mitogen-stimulated MNCs and modulate immune cells differentially, toward a more immune-suppressive phenotype.●There are a source-specific MSC-cytokine signatures upon interaction with immunocytes under mitogen-stimulated conditions.●This study gives scope for optimal use of MSCs from different sources for various indications in cellular therapy. Mesenchymal stromal cells (MSCs) are very advantageous in the field of regenerative medicine because of their immunomodulatory properties. However, reports show that these properties vary from source to source. Hence, understanding the source-dependent specificity of MSCs and their immunomodulatory abilities will enable optimal use of MSCs in cell-based therapies. Here, we studied 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 (hPBMCs/MNCs) and the concurrent changes in cytokine expression in MSCs, under mitogen-stimulated co-culture conditions. We used cytometric analysis to study the immunoregulatory properties of MSCs on MNCs and cytokine profiling of MSCs using a customized PCR array and solid-phase sandwich enzyme-linked immunosorbent assay. Our results reveal differential modulation of immune cells as well as MSCs upon activation by the mitogen phytohemagglutinin, independently and in co-culture. Notably, we observed source-specific MSC-cytokine signatures under stimulated conditions. Our results show that AT-MSCs up-regulate VEGF, BM-MSCs up-regulate PTGS-2 and WJ-MSCs increase expression of IDO considerably compared with controls. This remarkable modulation 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, our results highlight that MSCs sourced from different tissues may exhibit unique cytokine signatures and thus may be suitable for specific regenerative applications.