Comparison of in vivo immunomodulatory effects of intravenous and intraperitoneal administration of adipose-tissue mesenchymal stem cells in experimental autoimmune encephalomyelitis (EAE)

Due to their immunomodulatory and anti-inflammatory competence, mesenchymal stem cells (MSCs) have been considered as a suitable candidate for treatment of autoimmune diseases. Earlier studies have shown that treatment with bone marrow-derived MSCs may modulate immune responses and reduce disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we compare the immune regulatory properties of adipose tissue MSCs (AT-MSCs) in two independent routes of injection; namely intraperitoneal (IP) and intravenous (IV). We investigated the splenic CD4 + CD25 + FOXP3 + T cell population known as regulatory T cells, by flow cytometry and their brain cell infiltration by hematoxylin-eosin staining in both IP and IV routes of AT-MSC administration. We also evaluated the inflammatory cytokine profile including IFN-γ and IL-17 and anti-inflammatory cytokines such as IL-4 by ELISA technique in both routes of cell administration. We show that the IP route has a more pronounced effect in maintaining the splenic CD4 + CD25 + FOXP3 + T cell population and increase of IL-4 secretion. We also showed that IP injection of cells resulted in lower IFN-γ secretion and reduced cell infiltration in brain more effectively as compared to the IV route. The effects of AT-MSCs on down-regulation of splenocyte proliferation, IL-17 secretion and alleviating the severity of clinical scores were similar in IP and IV routes. Our data show that, due to their immunomodulative and neuroprotective effects, AT-MSCs may be a proper candidate for stem cell based MS therapy.