Abstract
ObjectivesA number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established.MethodsWe used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo.ResultsWe have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+).ConclusionOur results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures.
Highlights
A significant number of neurodegenerative diseases that affect the central nervous system progress with a loss of myelin
The mobilisation of endogenous neural/glial progenitor cells, the isolation of these cells, and their in vitro expansion and implantation in the same patient within the most invalidating of the chronic sclerotic multiple sclerosis (MS) plaques in the brain might be the most promising of approaches. This idea has been reinforced by a number of reports describing a pool of oligodendrocyte progenitor cells (OPCs) [3,4,5] within the parenchyma of the adult human brain, which might be responsible for the spontaneous myelination observed in patients with MS [6]
Primary cell cultures represent an invaluable model for testing the responsiveness of OPCs to drugs and growth factors, as well as for accurately defining the differentiation processes that result in fully functional oligodendrocytes
Summary
A significant number of neurodegenerative diseases that affect the central nervous system progress with a loss of myelin. The mobilisation of endogenous neural/glial progenitor cells, the isolation of these cells, and their in vitro expansion and implantation in the same patient within the most invalidating of the chronic sclerotic MS plaques in the brain might be the most promising of approaches. This idea has been reinforced by a number of reports describing a pool of oligodendrocyte progenitor cells (OPCs) [3,4,5] within the parenchyma of the adult human brain, which might be responsible for the spontaneous myelination observed in patients with MS [6]. Primary cell cultures represent an invaluable model for testing the responsiveness of OPCs to drugs and growth factors, as well as for accurately defining the differentiation processes that result in fully functional oligodendrocytes
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