The role of neural stem cells in regulating glial scar formation and repair

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.

Therapeutic potential of human stem cell transplantations for Vanishing White Matter: A quest for the Goldilocks graft

“…Therefore, effects of cell replacement therapy on cognitive recovery have not been assessed in this study. Similarly, although cell replacement therapy has been found to decrease neuroinflammation, 22,23 this was not investigated in the current study; neuroinflammation in the VWM brain is lacking in relation to the structural white matter damage, with meager astrogliosis, 5 axonal damage secondary to astrocytic pathology, 24 and no significant microglial activation 5,6 …”

MS-based glycomics: An analytical tool to assess nervous system diseases

“…Another indicator that commonly occurs in CNS diseases and injuries is the glial scar ( Nicaise et al, 2022 ). Recent studies have related glial scars to neurodegenerative disease including AD ( D’Ambrosi and Apolloni, 2020 ).…”

Modulating scar formation for improving brain repair: from coagulation and inflammation to cell therapy

“…The molecular mechanisms of NSC cell-fate determination and their cross-communication with glial and fibrotic scar cells are still insufficiently understood, but these will be instrumental for harnessing these cells as regenerative therapies in glial scar and brain repair. Nicaise et al ( 2021 ) review the pathobiology of the glial scar, the cellular components and extracellular matrix of the glial scar, and current findings on endogenous and exogenous NSCs in glial scar biology. They emphasize that, beside its trophic support, NSC transplantation could be beneficial in the resolution of the glial scar, possibly by targeting the metabolic machinery of myeloid cells.…”