Mesenchymal stem cells suppress infiltration of peripheral immune cells by down-regulating production of MCP-1 in the ischemic rat brain

Abstract

Mesenchymal stem cells (MSCs) have been shown to enhance the recovery of brain functions from the ischemic injury. In this study, we investigated the signaling molecules through which the grafted MSCs interact with damaged host brain and salvage the brain parenchyma from the secondary damages triggered by circulating immune cells. Transient occlusion of a middle cerebral artery induced the expression of proinflammatory cytokines such as MCP-1, TNFα, and IL-1β in the ischemic area. Transplantation of bone marrow-derived MSCs at postischemic day 3 reduced the expression of those cytokines and subsequent infiltration of invasive immune cells to the ischemic area. In vitro studies with anti MCP-1 antibody indicated that MCP-1 in ischemic brain extracts was primary signaling molecule that chemoattracted peritoneal macrophages. The MSC-conditioned could also block both MCP-1 expression and immune cell migration. The results suggest that immunomodulatory functions of MSCs are mediated through downregulation of MCP-1 expression