Abstract
Glial scars are a common pathological occurrence in a variety of central nervous system (CNS) diseases and injuries. They are caused after severe damage and consist of reactive glia that form a barrier around the damaged tissue that leads to a non-permissive microenvironment which prevents proper endogenous regeneration. While there are a number of therapies that are able to address some components of disease, there are none that provide regenerative properties. Within the past decade, neural stem cells (NSCs) have been heavily studied due to their potent anti-inflammatory and reparative capabilities in disease and injury. Exogenously applied NSCs have been found to aid in glial scar healing by reducing inflammation and providing cell replacement. However, endogenous NSCs have also been found to contribute to the reactive environment by different means. Further understanding how NSCs can be leveraged to aid in the resolution of the glial scar is imperative in the use of these cells as regenerative therapies. To do so, humanised 3D model systems have been developed to study the development and maintenance of the glial scar. Herein, we explore the current work on endogenous and exogenous NSCs in the glial scar as well as the novel 3D stem cell–based technologies being used to model this pathology in a dish.
Highlights
The high complexity of the central nervous system (CNS) leads to its limited ability to recover upon damage, mainly due to the scarce regenerative potential
Targeted inhibition of notch signalling, using an inducible deletion of the Notch intracellular domain co-transcriptional activator, RBPJκ, in nestin positive cells resulted in a marked shift of neural stem cells (NSCs) fate in the subventricular zone (SVZ) from the astrocyte lineage towards the generation of neuroblasts which resulted in defective glial scar formation and enhanced microvascular haemorrhaging at 14 days after injury (Benner et al 2013)
Rodent studies tracing endogenous NSCs in injuries and disease have revealed diversified roles for these cells depending on the model system
Summary
The high complexity of the central nervous system (CNS) leads to its limited ability to recover upon damage, mainly due to the scarce regenerative potential. In MS, the initial injury is triggered by adaptive immune responses, wherein the infiltration of peripherally activated inflammatory T cells attacks oligodendrocytes resulting in the further activation of astrocytes and microglia and leading to the formation of a glial scar (or lesion) (Bribian et al 2018).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
