![]() ![]() Nowadays, therapeutic approaches aim to treat acute attacks and to improve symptoms. In particular, B cells’ role in MS is not limited to the antibody production, but a main role is played by their antibody-independent functions, which are the antigen presentation to T cells and the modulation of T and myeloid cell function through the secretion of cytokines. Even if MS was for a long time considered as a T cell-mediated disease, the positive effects exerted by antibodies targeting CD20, highlighted the role of B cells in the immunopathogenesis of MS. In addition, in the demyelinated areas, resident microglia and macrophages are also present. T lymphocytes, both CD4+ T cells and CD8+ T cells, take part in the pathological process, and in particular MS is triggered by pathogenic T helper (Th) 17, Th1, and CD8+ autoreactive T lymphocytes directed against myelin components. MS is based on an autoimmune mechanism, and specifically the myelin antigens represent the targets. About three million people are affected by MS, and in particular, females are more affected than males. RRMS shows an earlier onset, appearing typically between 20-35 years of age, while PPMS at about 40 years of age. Only a small number of patients has a progressive disease course since the onset, indicating a primary progressive MS (PPMS). After, the development of permanent neurological deficits and the progression of clinical disability become prominent, indicating a secondary progressive MS (SPMS). In the majority of patients, reversible episodes of neurological deficits, indicated as relapses, characterize the initial phases of the disease, that is indicated as relapsing remitting MS (RRMS). Clinically isolated syndrome (CIS) is indicated as the first clinical manifestation of the disease, showing features of inflammatory demyelination, but the MS criteria are not completely fulfilled. The hallmark of the pathology is the accumulation of demyelinating lesions both in white and grey matters in the brain and spinal cord. Multiple sclerosis (MS) represents a chronic inflammatory, demyelinating, neurodegenerative disease of the central nervous system (CNS). Clinical trials highlighted the safety and feasibility of MSC administration and reported some improvements, but other trials using larger cohorts of patients are needed. Secretome, both conditioned medium and EVs, also showed protective effects in MS models and appeared promising to develop new approaches. Moreover, MSCs engineered to express different genes, preconditioned with different compounds, differentiated or in combination with other compounds also exerted beneficial actions in MS models, in some cases also superior to native MSCs. Experimental models of MS evidenced that MSCs were able to reduce inflammatory cell infiltration and disease score. ![]() In this review, we focused on studies performed on in vivo MS models involving the administration of MSCs and on clinical trials evaluating MSCs administration. The secretome is represented by growth factors, cytokines, and extracellular vesicles (EVs) released by MSCs. Stem cell therapy using mesenchymal stem cells (MSCs) appeared promising in different neurodegenerative conditions, thanks to their beneficial capacities, including the immunomodulation ability, and to their secretome. Nowadays, available therapies for MS can help to manage MS course and symptoms, but new therapeutic approaches are required. Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. ![]()
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