Immunomodulatory Effects of Mesenchymal Stem Cells on T- and B-Cells in a Quiescent State in a Chronic Experimental Model of Autoimmune Encephalomyelitis

Resumen

Introduction: Multiple sclerosis (MS) is an immune-mediated disease affecting the central nervous system (CNS). Many drugs have been tested in animal models of MS (e.g., Experimental Autoimmune Encephalomyelitis (EAE)). Nevertheless, clinical observations indicate that suppression of the immune response is a very simple approach to address the problem, since the injuries produced by the inflammation do not predict later changes. An emerging strategy for neuroprotection and remyelination is the transplantation of stem cells. Mesenchymal stem cells (MSC) have been characterized by their multipotentiality and their capacity for immunomodulation, thus raising great expectations in regenerative medicine. Materials and Methods: In this context, we have tested the therapeutic potential of intravenously injected bone marrow-MSC from healthy rat donors in a chronic EAE model using Lewis 1A rats. We analyzed the role of MSC on T- and B-cells in the quiescent state. Results: Rat MSC expressed the vascular cell adhesion molecule CD106 to a slight extent. MSC promoted T- or B-lymphocyte survival but did not modify the T- or B-lymphocyte cell cycles in the quiescent state. Our results also confirm that MSC modulate EAE though the production of soluble cytokines. In vitro, MSC decreased the EAE by immunomodulating the Th1/Th2 response. Moreover, MSC controlled CD27/CD86 expression in different ways. Conclusion: Animals infused with MSC prior to the EAE immunization did not develop EAE, or their EAE clinical scores were decreased, whereas animals that received MSC after the induction of EAE developed a normal EAE course. This novel therapeutic strategy would further our knowledge of the pathophysiology of autoimmune diseases, which in the future could be translated into clinical application.