Differentiation of human olfactory bulb‐derived neural stem cells toward oligodendrocyte

Abstract

In the central nervous system (CNS), oligodendrocytes are the glial element in charge of myelin formation. Obtaining an overall presence of oligodendrocyte precursor cells/oligodendrocytes (OPCs/OLs) in culture from different sources of NSCs is an important research area, because OPCs/OLs may provide a promising therapeutic strategy for diseases affecting myelination of axons. The present study was designed to differentiate human olfactory bulb NSCs (OBNSCs) into OPCs/OLs and using expression profiling (RT-qPCR) gene, immunocytochemistry, and specific protein expression to highlight molecular mechanism(s) underlying differentiation of human OBNSCs into OPCs/OLs. The differentiation of OBNSCs was characterized by a simultaneous appearance of neurons and glial cells. The differentiation medium, containing cAMP, PDGFA, T3, and all-trans-retinoic acid (ATRA), promotes OBNSCs to generate mostly oligodendrocytes (OLs) displaying morphological changes, and appearance of long cytoplasmic processes. OBNSCs showed, after 5 days in OLs differentiation medium, a considerable decrease in the number of nestin positive cells, which was associated with a concomitant increase of NG2 immunoreactive cells and few O4(+)-OPCs. In addition, a significant up regulation in gene and protein expression profile of stage specific cell markers for OPCs/OLs (CNPase, Galc, NG2, MOG, OLIG1, OLIG2, MBP), neurons, and astrocytes (MAP2, β-TubulinIII, GFAP) and concomitant decrease of OBNSCs pluripotency markers (Oct4, Sox2, Nestin), was demonstrated following induction of OBNSCs differentiation. Taken together, the present study demonstrate the marked ability of a cocktail of factors containing PDGFA, T3, cAMP, and ATRA, to induce OBNSCs differentiation into OPCs/OLs and shed light on the key genes and pathological pathways involved in this process.

Human Olfactory Bulb Neural Stem Cells (Hu-OBNSCs) Can Be Loaded with Paclitaxel and Used to Inhibit Glioblastoma Cell Growth

“…Removal of the mitogen triggered their differentiation into GFAP-positive astrocytes and MAP-2-positive neurons. These findings are in harmony with our previous studies [3,4,21,22,23,24,25,26], and clearly indicate the stem cell nature of isolated Hu-OBNSCs, based on their multipotent potential and their ability to differentiate into the different cells types forming nervous tissues.…”

Neural Stem Cells in the Adult Olfactory Bulb Core Generate Mature Neurons in Vivo

“…[23][24][25][26][27][28][29][30][31] Furthermore, it has been reported that cells derived from the human OB give rise to neurons and glia in cell culture. [32][33][34][35][36][37] However, the precise location, features, and most importantly, the full neurogenic potential of these NSCs in vivo has yet to be defined.…”

Saikosaponin‐d improved the stemness of mouse neural stem cells and increased their thermotolerance potential

“…The SOX2 gene, which is one of the genes that are crucial for maintaining the undifferentiated state, and the OCT4 (Marei et al., 2011), which is one of the “major” genes controlling self‐renewal, were both significantly overexpressed in our test. Combined with the monoclonal spherical growth state of NSCs, we speculated that Ssd treatment can increase the stemness of NSC and maintain the pluripotent state (Marei et al., 2018). It can be seen that when NSCs are in the inhibitory state of proliferation and differentiation, their ability to resist the adverse external environment is significantly enhanced.…”