Recent advances in endogenous neural stem/progenitor cell manipulation for spinal cord injury repair

Theranostics, 2023 · DOI: 10.7150/thno.84133 · Published: July 9, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Traumatic spinal cord injury (SCI) leads to neurological impairments with limited treatment options. A promising strategy involves recruiting and facilitating the differentiation of endogenous neural stem/progenitor cells (eNSPCs) towards neurons. After SCI, eNSPCs tend to become astrocytes rather than neurons, hindering neuronal regeneration. Manipulation approaches aim to enhance neurogenesis capacity and reconstruct the microenvironment through pharmacological treatments, exosomes, gene therapy, scaffolds, and inflammation regulation. Combined treatments are highlighted for their potential to address the complex challenges of SCI, providing clues for future investigations into spinal cord injury repair.

Study Duration

Not specified

Participants

Various SCI models

Evidence Level

Review

Key Findings

1
The post-SCI microenvironment promotes the proliferation and astrocyte differentiation of eNSPCs, contributing to glial scar formation.
2
Strategies to promote neurogenesis of eNSPCs include boosting intrinsic proliferation/differentiation capacity and remodeling the hostile microenvironment.
3
Combined treatments, leveraging biocompatible materials, synergistically address multifaceted challenges in SCI, achieving impressive outcomes in rodent and canine models.

Research Summary

This review introduces the pathological changes of eNSPCs and their microenvironment after SCI. It focuses on strategies developed to stimulate eNSPC neurogenesis and relieve inhibiting elements, particularly combinational treatments. Efforts to promote neural circuit formation through manipulation of eNSPCs aim to boost intrinsic capacity and remodel the hostile microenvironment via pharmacological treatments, exosome administration, gene therapy, scaffold implantation, inflammatory regulation, and inhibitory element delineation. Combined strategies address multifaceted challenges by evoking the intrinsic regeneration mechanism of eNSPCs and providing a permissive environment, demonstrating locomotion and sensory behavioral recovery in SCI models.

Practical Implications

Therapeutic Target Identification

Identifying and manipulating key molecular pathways (Wnt, BMP, Notch) can promote neuronal differentiation of eNSPCs.

Combined Therapies

Combining pharmacological, gene, and material-based approaches can synergistically improve SCI outcomes.

Microenvironment Modulation

Targeting inflammation and inhibitory molecules (MAIs, CSPGs) creates a permissive environment for neurogenesis.

Study Limitations

1
Ongoing debate regarding suitable sources of eNSPCs in the adult spinal cord.
2
The critical regulators that modulate their dynamic response after injury remain to be elucidated.
3
The heterogeneity within the eNSPC pool is another crucial issue that needs to be addressed.

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