Identification and characterization of the Neural Stem/Progenitor Cell population in the Adult Human Brain Meninges

Background and aim Meninges are three membrane layers coverings of the brain. Meninges host several different cell types and are widely distributed in the central nervous system (CNS). Besides protection they also play an important role during brain development and neurological pathologies. Several studies highlight the presence of stem/progenitor cells in murine meninges contributing to formation of brain neural cells during perinatal development and in adult following different pathological conditions. The aim of this work was to assess whether similar population of stem/progenitor cell were present also in adult human brain meninges. Methods, results and conclusions We studied both adult and fetal human brain meninges by immunofluorescence and RNAscope analysis and found cells expressing neural stem/precursor markers, including SOX2, nestin and doublecortin (DCX). As further confirmation, we in vitro isolated and cultured adult human brain meningeal cells and assessed the stem and neural differentiation potential of the cultured cell. In vitro expanded meningeal neural stem/progenitor cells present stem cell features, including expandability (growth curve), self-renewal (colony forming unit assay) and express several markers of neural undifferentiated cells, including SOX2, nestin and doublecortin. Moreover, we efficiently differentiate in vitro cultured adult human meningeal cells into mature neurons, expressing MAP2 and NeuN markers, and mature oligodendrocytes, expressing GALC and MBP markers. Of note, human neurons derived from adult human meningeal neural stem/precursor are capable to sustain action potential measured by patch clamp recording. Adult human meningeal neural stem/precursor cells show neural differentiation potential also in vivo. After injection in 8-weeks-old mice hippocampus, meningeal neural stem/precursor cells survive, express neural undifferentiated marker at 4 weeks post transplantation and are able to differentiate in mature neurons after 8 weeks. Although the role of neural stem/precursor cells in adult human brain meninges remain to be explored, our data collectively demonstrate that meninges can be considered as a new source of neural stem/precursor cells. These cells might represent a potential new neural stem/precursor cell source that can be exploited both to treat neurodegenerative diseases and to increase the understanding of adult human brain plasticity.