Marco Milanese
University of Genoa, Italy
Title: MicroRNAs shuttled by extracellular vesicles derived from mesenchymal stem cells rescue glial activation in in-vitro models of amyotrophic lateral sclerosis
Biography
Biography: Marco Milanese
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease characterized by the selective death of upper and lower motor neurons (MNs). The mechanism of MN damage and death has been ascribed to several cellular and molecular alterations, including neuro inflammation. ALS is also a non-cell-autonomous disease, due to the contribution of glial cells, such as astrocytes and microglia that secrete neurotoxic factors and promote a noxious environment for MN. At present there is no effective cure for ALS. We previously demonstrated that intravenous administration of bone marrow mesenchymal stem cells (MSCs), prolonged survival probability, improved motor functions and ameliorated pathological features, including gliosis and neuro inflammation, in the spinal cord of the SOD1G93A mouse model of ALS. There is a consensus supporting that the beneficial outcomes of MSCs are unlikely due to trans-differentiation, but possibly to paracrine effects, thus we postulated that one of these mechanisms could be the transfer to target cells of microRNAs (miRNAs) shuttled by extracellular vesicles (EVs) isolated from the secretome of MSCs. To this aim we studied the activity of MSCs-derived EVs both on astrocytes isolated from the spinal cord of symptomatic SOD1G93A mice and human astrocytes (iAstrocytes) differentiated from inducible neural progenitor cells (iNPCs) of ALS patients.