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

Cell and Tissue Research, 2022 · DOI: https://doi.org/10.1007/s00441-021-03554-0 · Published: November 25, 2021

Regenerative Medicine Neurology Genetics

Simple Explanation

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. 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. 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.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Endogenous NSCs can contribute to reactive gliosis by differentiating into reactive astrocytes, while in other models, they can provide new myelination and neural replacement.
2
Exogenous NSCs are anti-inflammatory and promote trophic support via the secretion of factors, including IL-4, IL-13, and NGF, and can provide neuronal replacement and promote myelin repair.
3
3D stem cell model systems allow for a more targeted in vitro analysis on the exact structure and molecular makeup of this pathology, including inhibitor ECM proteins on scaffolds.

Research Summary

Rodent studies tracing endogenous NSCs in injuries and disease have revealed diversified roles for these cells depending on the model system. In SCI-based models, many endogenous NSCs have been found to contribute to astrocyte reactivity within the scar via differentiation. Interestingly exogenous NSC therapy has provided much better results in the healing of the scar. Transplanted NSCs have been shown to overcome the inflammatory milieu and engraft where they provide neurotrophic and anti-inflammatory support to the damaged tissue. Towards a better understanding of the glial scar in injury as well as disease, 3D stem cell model systems have been developed. Herein, human stem cells have been able to be differentiated into a multitude of cells found within the scar, allowing for a more targeted in vitro analysis

Practical Implications

Targeted Therapies

Targeting specific astrocyte subtypes that negatively influence the regenerative capacity of the glial scar may result in the greatest benefit for patients.

Delivery Methods

The method of cell delivery in relation to the glial scar plays a key role in graft survival and integration, with surface transplantation showing superior outcomes.

Metabolic Targeting

NSC transplantation could be beneficial in the resolution and regeneration of the glial scar, possibly by targeting the metabolic machinery of myeloid cells.

Study Limitations

1
Limited regenerative potential of endogenous NSCs with age.
2
Tumorigenic potential and genome instability of iPSC-NSCs.
3
Challenges in accurately modeling the complex 3D nature of the glial scar in standard 2D in vitro systems.

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