Insights into the Biology and Therapeutic Applications of Neural Stem Cells

Abstract

The cerebral cortex is essential for our higher cognitive functions and emotional reasoning. Arguably, this brain structure is the distinguishing feature of our species, and yet our remarkable cognitive capacity has seemingly come at a cost to the regenerative capacity of the human brain. Indeed, the capacity for regeneration and neurogenesis of the brains of vertebrates has declined over the course of evolution, from fish to rodents to primates. Nevertheless, recent evidence supporting the existence of neural stem cells (NSCs) in the adult human brain raises new questions about the biological significance of adult neurogenesis in relation to ageing and the possibility that such endogenous sources of NSCs might provide therapeutic options for the treatment of brain injury and disease. Here, we highlight recent insights and perspectives on NSCs within both the developing and adult cerebral cortex. Our review of NSCs during development focuses upon the diversity and therapeutic potential of these cells for use in cellular transplantation and in the modeling of neurodevelopmental disorders. Finally, we describe the cellular and molecular characteristics of NSCs within the adult brain and strategies to harness the therapeutic potential of these cell populations in the treatment of brain injury and disease.

Figure 1

Summary of progenitor subtype diversity within the rodent and human/primate brain. Apical Progenitor (AP) cells (light blue) include apical Radial Glia (aRG) which attach to the basal lamina and apical Intermediate Progenitor (aIP) cells which have short processes. Both types of APs are defined by their mitotic division at the apical surface. Subapical Progenitor (SAP) cells (coloured green) are defined by their ventricular contact and abventricular mode of cell division. Basal Progenitor (BP) cells (magenta) are defined by their basal mitoses and comprise basal Radial Glia (bRG) cells attached to the basal lamina as well as basal Intermediate Progenitor (bIP) cells which undergo a proliferative division (labelled “P”) or neurogenic divisions (labelled “N”), as indicated. A yellow coloured marginal zone progenitor is represented in rodent cortex. In the human/primate cortex, AP and SAP cell types have been identified, while three types of bRGs have been identified including those with a basal attachment, an apical attachment, or only emanating short processes. The bIPs cell types which undergo proliferative or neurogenic divisions have been described in the iSVZ and oSVZ. The presence of MZ progenitor cells within the human/primate cortex remains to be clarified. VZ: ventricular zone, SVZ: subventricular zone, IZ: Intermediate Zone, CP: cortical plate, MZ: marginal zone, iSVZ: inner subventricular zone, and oSVZ: outer subventricular zone as presented. Relative sizes of rodent and human/primate compartments are not drawn to scale. See text for further details.

Figure 2

Summary of the promise, priorities, problems, and progress of the therapeutic application of NSCs. This schematic outlines the promise of the therapeutic application of NSCs, several of the priorities for applying NSCs for therapeutic application, some of the problems faced with using NSCs in patients, and finally what progress that has been made in the application of NSCs.