Elena R. Andreeva
Institute of Biomedical Problems
Russia
Title: Activated Leukocytes Alter Allogeneic Multipotent Mesenchymal Stromal Cell Functions
Biography
Biography: Elena R. Andreeva
Abstract
Multipotent mesenchymal stromal cells (MSCs) have been assumed as a perspective tool for allogeneic application in cell therapy due to their immunotolerance. Recent findings reveal that MSCs are not totally invisible for host immune system but rather possess immuno-evasive properties. Here we evaluated the direct cell-to-cell and paracrine effects of PHA-activated mononuclear cells (MNCs) from peripheral blood on allogeneic MSCs at standard (20%) and tissue-related (5%) O2 levels. Interaction with MNCs had no effect on MSC stromal phenotype, but significantly increased soluble and membrane-associated ICAM-1 expression. Upon direct contact MNCs modulated the functional activity of MSCs: the viability of MSCs with elevated ROS was reduced. ROS formation, mitochondrial trans-membrane potential and lysosome activity were increased. MSC proliferation and differentiation was slowed down. Paracrine regulation of MNC/MSCs interaction did not affect MSC intracellular parameters, but suppressed its migration. The global gene expression analysis showed that MSCs were more sensitive to the MNCs at 20% O2. MSC "proinflammatory" activation was associated with increased expression of IL-8, CCL5,IL-1b,COX-2. MCP-1,IL-1b,TRAF3IP2 were up regulated, and IL-8,COX-2,IL-7R – down regulated at 5% O2 in comparison with 20% O2. Upon interaction with MNCs the up-regulation of "immunosuppressive" genes: HLA-B,-E,-F,-H, PTGIS, TGFBI, LIF, PTGS2 was detected. Increased expression of genes whose products provide MSC proliferative activity, extracellular matrix remodeling (MMP1,MMP3) were also demonstrated. These data indicate that the interaction with MNCs significantly altered MSC gene profile and functional activity that can further facilitate the MSC participation in regenerative processes in tissues.