Regulating Endogenous Neural Stem Cell Activation to Promote Spinal Cord Injury Repair

Abstract

Spinal cord injury (SCI) affects millions of individuals worldwide. Currently, there is no cure, and treatment options to promote neural recovery are limited. An innovative approach to improve outcomes following SCI involves the recruitment of endogenous populations of neural stem cells (NSCs). NSCs can be isolated from the neuroaxis of the central nervous system (CNS), with brain and spinal cord populations sharing common characteristics (as well as regionally distinct phenotypes). Within the spinal cord, a number of NSC sub-populations have been identified which display unique protein expression profiles and proliferation kinetics. Collectively, the potential for NSCs to impact regenerative medicine strategies hinges on their cardinal properties, including self-renewal and multipotency (the ability to generate de novo neurons, astrocytes, and oligodendrocytes). Accordingly, endogenous NSCs could be harnessed to replace lost cells and promote structural repair following SCI. While studies exploring the efficacy of this approach continue to suggest its potential, many questions remain including those related to heterogeneity within the NSC pool, the interaction of NSCs with their environment, and the identification of factors that can enhance their response. We discuss the current state of knowledge regarding populations of endogenous spinal cord NSCs, their niche, and the factors that regulate their behavior. In an attempt to move towards the goal of enhancing neural repair, we highlight approaches that promote NSC activation following injury including the modulation of the microenvironment and parenchymal cells, pharmaceuticals, and applied electrical stimulation.

UAMC-3203 improves the inhibitory microenvironment to repair spinal cord injury by inhibiting ferroptosis

“…Inhibitory factors existed in the microenvironment after SCI may affect endogenous stem cell differentiation [20], including astrocytes and microglia. Microglia are resident macrophages that normally remain static in the central nervous system [21].…”

Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment

“…Irreversible neuronal loss occurs at the injury site ( Yates et al, 2019 ; Dias et al, 2021 ). Glial scars, of which reactive astrocytes are a major component, are thought to play a dual role in spinal cord repair ( Adams and Gallo, 2018 ; Yang et al, 2020a ; Gilbert et al, 2022 ), and it is now believed that a modest reduction in glial scar density is important for repair of the injured spinal cord ( Hackett et al, 2018 ; Hesp et al, 2018 ; Yang et al, 2020b ).…”

Neural Stem Cells Overexpressing Arginine Decarboxylase Improve Functional Recovery from Spinal Cord Injury in a Mouse Model

“…Grafted cells can provide trophic support for neurons and manipulate the environment within the damaged spinal cord to facilitate axonal regeneration or promote plasticity [ 9 , 11 , 12 ]. Sources for cell transplantation are typically multipotent stem cells, including embryonic stem cells (ESCs) [ 15 , 16 ], neural stem cells (NSCs), neural precursor cells (NPCs) [ 13 , 17 , 18 , 19 ], induced pluripotent stem cells (iPSCs) [ 20 ], and mesenchymal stem cells (MSCs) [ 21 ]. Of these, NSCs and NPCs have been the most effective in treating CNS diseases [ 13 , 17 , 22 ].…”