Adipose tissue derived mesenchymal stem cells exhibit a superior immune-modulatoery effect on mature dendritic cells compared to bone marrow derived mesenchymal stem cells

Abstract

Background & Aim Background The ability of mesenchymal stem cells (MSCs) to interact with immune cells and exert a modulatory effect is the core of cellular therapy approaches. Dendritic cells (DCs), the most potent of antigen presenting cells (APCs), play a key role in T-cell activation and firing immune responses. The direct interaction between MSCs and mature DCs (mDCs) results in attenuation of mDCs' activity and subsequent immune reactions. Aim Bone marrow derived MSCs (BM-MSCs) and adipose tissue derived MSCs (AT- MSCs), are more abundant and easier to harvest compared to other types of MSCs. How BM-MSCs and AT-MSCs affect mDCs can be illustrated with changes in surface marker expression and mDCs secreted cytokines, a focus is needed on changes in mDC gene expression which may help in a better understanding of the interaction process. Methods, Results & Conclusion Methods MSCs were isolated from two adult sources bone marrow and adipose tissue. Monocytes were isolated from peripheral blood to generate mDCs in recommended culture conditions. All cells were characterized by flowcytometry. Multiplex immunoassay was carried out to evaluate the inflammatory cytokines levels. PCR arrays were performed to demonstrate the gene expression profile of mDCs. All tests were performed before and after direct contact co-culture of mDCs with BM-MSCs, and with AT-MSCs. Results The immune-inhibitory effect of both types of MSCs on mDCs was manifested by a decrease in the levels of inflammatory cytokines, and the downregulation of 84 investigated genes responsible for mDC activity in both co-cultures. The fold changes, and fold change ratios from PCR array data clearly demonstrate the superiority of AT-MSCs in inhibiting mDCs immune awakening functions. This finding is supported by previous microarray analysis of the inherent immune-modulatory potential of both types of MSCs, which revealed an advantage for AT-MSCs over BM-MSCs, in terms of the expression magnitude of immune-regulatory genes. Functional annotation clustering and gene ontology demonstrated that all investigated genes participate in response to stimulus (p- value= 4.3 E-26), and that 79.8% (67 out of 84 genes) are significant players in positive regulation of response to stimulus (p-value = 4.3 E-45). Conclusion These findings highlight the outcome of MSCs’ interaction with mDCs on the molecular level. Our data confirm the immune-modulatory properties of MSCs and suggest AT-MSCs as a more effective suppressor of mDCs immune activity than BM-MSCs.