Abstract
Multiple Sclerosis (MS) is a devastating autoimmune disease of the central immune system (CNS). MS is caused by the autoreactivity of the immune system against self-antigens, which causes the demyelination of the nerve cells and inflammation in the CNS. These events can cause permanent neurological damages and lead to severe disabilities. The goal of the current project was to assess the immunomodulatory potential of human placenta-derived mesenchymal stromal cells (PMSCs) and their secreted exosomes (PMSC-Exos) in the context of MS. The placenta is a unique source of MSCs. This organ is composed of maternal and fetal components that can maintain immunotolerance against the mother’s and child’s immune system. This unique characteristic certainly contributes to the PMSCs’ immunoregulatory potential and make them the ideal candidate to treat autoimmune disease. Human PMSCs isolated from the chorionic villus tissue of placenta have been extensively characterized. PMSCs secrete several growth factors and cytokines that possess both neuroprotective and immunomodulatory functions. In vitro studies have shown that both PMSCs and PMSC-derived exosomes have neuroprotective capabilities. In vivo studies in an in-utero myelomeningocele (spina bifida) ovine model, demonstrated that PMSCs can rescue motor neurons and alleviate the spinal cord defect associated with the disease. In addition to growth factors and bioactive mediator PMSCs also secrete exosomes that are extra cellular vesicles containing several key proteins, mRNAs and miRNAs involved in neuroprotective, immunomodulatory and angiogenic functions. PMSC-derived exosomes have been demonstrated to possess neuroprotective capabilities in an in vitro neuroprotection model. To date, the immunomodulatory potential of human placenta-derived mesenchymal stromal cells and their secreted exosomes in the context of an autoimmune disorder have not been extensively explored.
The goal of this research project was to focus on the immunomodulatory effects of human PMSCs and PMSC-Exos in in vitro and in vivo studies. In vitro studies demonstrated that PMSCs can suppress leukocyte proliferation through a predominantly contact mediated mechanism. PMSC-Exos, at several concentrations, did not display immunosuppressive effects suggesting these particles alone may not elicit immunoregulatory properties. To study the immunomodulatory functions of PMSCs and PMSC-Exos in vivo, we utilized the established MOG-peptide induced experimental autoimmune encephalomyelitis (EAE) mice model, which is widely used as a translational model of multiple sclerosis. Preliminary data has demonstrated that application of PMSCs and PMSC-Exos influence Treg induction in EAE mice.
In summary, we have demonstrated that PMSCs and PMSC-Exos have immunomodulatory capabilities and have the potential to be used for treating immune disorders in the future.