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  4. Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury

Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury

Cells, 2023 · DOI: 10.3390/cells12202499 · Published: October 20, 2023

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

Spinal cord injury (SCI) affects millions worldwide, and current treatments often fail to fully restore lost function. New approaches using stem cells to create neural progenitor cells (NPCs) are promising. These NPCs can be transplanted to the injury site to help regenerate the spinal cord. Direct reprogramming, which converts non-neuronal cells into NPCs without going through a pluripotent state, is a particularly attractive strategy. This method allows for the production of large numbers of NPCs in the lab for transplantation. However, a major challenge is the low efficiency of direct reprogramming, which hinders its use in clinics. This review explores new targets, tools, and approaches, like mechanotransduction and electrical stimulation, to improve reprogramming efficiency for spinal cord injury treatment.

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review

Key Findings

  • 1
    The review highlights novel targets for improving direct pro-neural reprogramming, including mitochondria, nucleoli, and G-quadruplexes.
  • 2
    It discusses various tools and approaches to enhance reprogramming efficiency, such as mechanotransduction and electrical stimulation.
  • 3
    The review emphasizes the potential of directly reprogrammed neural progenitor cells (drNPCs) as a therapeutic strategy for spinal cord injury due to their lower tumorigenic risk compared to iPSCs and faster pro-neuronal differentiation.

Research Summary

This review focuses on improving the efficiency of direct pro-neural reprogramming as a potential aid for neuroregeneration in spinal cord injury (SCI). It overviews recent literature on reprogrammed cells for SCI, summarizes existing approaches to enhance direct reprogramming to pro-neuronal lineage, and proposes possible approaches yet to be tested. The review concludes that directly reprogrammed pro-neuronal cells hold clinical potential, especially when combined with other therapeutic tools, and that enhancing the efficacy of cell fate conversion could bolster the translational applications of drNPCs.

Practical Implications

Clinical Translation

Improving the efficiency of direct pro-neural reprogramming could lead to more effective cell-based therapies for spinal cord injury.

Target Identification

Identifying novel targets like mitochondria, nucleoli, and G-quadruplexes can open new avenues for therapeutic intervention.

Combination Therapies

Combining drNPCs with tissue-engineered scaffolds and bioactive molecules may enhance cell survival and differentiation in the injury site.

Study Limitations

  • 1
    Low efficiency of pro-neural reprogramming remains a hurdle.
  • 2
    Survival rate of transplanted progenitor cells in the damaged tissue is relatively low.
  • 3
    Differentiation of transplanted cells towards astroglia in the inflamed tissue microenvironment.

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