Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Abstract

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

“…However, few 3D platforms have been applied to the study of cell replacement therapies, or transplantation, which offer exciting possibilities to treat adult retinopathies [ 72 ]. While transplantation relies upon SC abilities to differentiate and infiltrate host tissue (reviewed in [ 73 ]), few projects have examined the motility of replacement cells in response to externally applied cues, despite the significance of their spatial positioning within host tissue.…”

Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

“…In contrast, gene delivery to NSPCs stimulates endogenous neuro- and gliogenesis by activating the factors necessary to promote proliferation, differentiation, integration, or migration of target cells and progeny. Endogenous NSPC populations in the adult mammalian CNS include Nestin+ neural stem cells, NG2+ polydendrocytes, Sox2+, and ependymal progenitors [ 59 ]. Gene delivery to these populations has recently resulted in enhanced functional locomotor recovery, e.g., Gsx1 [ 143 ] and Sox2 [ 147 ].…”

“…Immediately after SCI, NSPC populations transition from quiescent to the activated state, e.g., neural stem cells, ependymal progenitors, and OPCs/NG2 polydendrocytes [ 59 ]. Activated NSPCs proliferate and differentiate into glial lineage cells and contribute to the formation of the glial scar border [ 22 , 27 , 28 ].…”

“…Ependymal cells contribute to few clinical injury types due to low migratory capacity even in an activated state. However, in stab and contusion SCI, ependymal cells become activated, revert to a stem-cell-like state, and contribute to astrocyte population due to central canal damage [ 59 ]. Ependymal progenitors are thus a popular target for regenerative therapies.…”

“…This NSPC population is spatially distributed in a checker-like pattern throughout the mammalian spinal cord. Thus, this population contributes to the glial scar of various SCI types and grades due to distribution and migratory capacity [ 59 ]. NG2 polydendrocytes natively possess qualities of their differentiated progeny, e.g., hypertrophy and secretion of inhibitory molecules that inhibit axogenesis.…”