Isolation and in-vitro Characterization of the Adult Neural Stem/Progenitor Cells from the Human Brain Meninges

We recently identify in rodent brain meninges a population of neurogenic cell that, during the perinatal stages, without proliferation, migrate from meninges to the cortex and differentiated into functional cortical neurons integrated with the microenvironment. Several studies further confirm the presence of stem/progenitor cells in meninges contributing to formation of brain neural cells in different pathological conditions. In this work, we asked whether a population of stem/progenitor cell were present also in adult human brain meninges considering that the presence of adult neurogenesis in humans is highly debated. We describe the presence of cells expressing neural stem/precursor markers in both adult and fetal human brain meninges. We were able to confirm the presence of neuronal precursor markers, including DCX, as protein in immunofluorescence and as RNA molecules by using the RNAscope in situ hybridization. As further confirmation, we in vitro cultured adult human meningeal cells and assessed their stem and neural differentiation potential. In vitro expanded meningeal neural stem/progenitor cells present stem cell features, including self-renewal. Moreover, from in vitro cultured adult human meningeal cells, we efficiently obtained mature neurons and oligodendrocytes. We observed the presence of MAP2 and NeuN positive cells, that show neuronal electrophysiological properties. Adult meningeal neural stem/precursor cells show differentiation potential also in vivo. After injection in the mice hippocampus, meningeal neural stem/precursor cells survive and are able to differentiate in mature neurons. 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. Considering that the meninges cover the brain, these cells are relatively accessible and might represent a potential new neural stem/precursor cell source that can be exploited in several neurodegenerative diseases.