Because of their unique attributes of plasticity and accessibility, bone marrow-derived mesenchymal stem cells (MSCs) may find use for therapy of neurodegenerative disorders. Our previous studies of adult human MSCs demonstrated that these cells express an extensive assortment of neural genes at a low but clearly detectable level. Here, we report expression of 12 neural genes, 8 genes related to the neuro-dopaminergic system, and 11 transcription factors with neural significance by human MSCs. Our results suggest that, as opposed to cells that do not express neural genes, human MSCs are predisposed to differentiate to neuronal and glial lineages, given the proper conditions. Our findings add a new dimension in which to view adult stem cell plasticity, and may explain the relative ease with which MSCs, transplanted into the central nervous system (CNS) differentiate to a variety of functional neural cell types. Our results further promote the possibility that adult human MSCs are promising candidates for cell-based therapy of neurodegenerative diseases.
DJ-1 plays an important role in oxidative stress, and is involved in various neurodegenerative diseases. Accumulating evidence suggests a central role for oxidative stress in multiple sclerosis (MS). The aim of this study was to examine whether changes occur in DJ-1 expression in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and protein expression levels in EAE and a correlation between disease severity and increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells. Immunocytochemical staining demonstrated that DJ-1 is present both in the cytoplasm and the nuclei of these cells. This is the first report of modulation of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar results were observed in glioma cells exposed to ROS. In view of the accumulating evidence on the central role of oxidative stress in MS, and the importance of DJ-1 in oxidative stress management by the CNS, we believe that DJ-1 will be found to have a central role in MS.
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