Metabolic Reprogramming of Neural Stem Cells by Chiral Nanofiber for Spinal Cord Injury

ACS Nano, 2025 · DOI: https://doi.org/10.1021/acsnano.4c15770 · Published: January 22, 2025

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This research explores a new method for treating spinal cord injuries (SCI) using neural stem cells (NSCs). It focuses on improving how these cells repair damaged neural circuits by controlling their metabolism with a special biomaterial. The study introduces a biomimetic dextral hydrogel (DH) with right-handed nanofibers. This hydrogel reprograms the lipid metabolism of NSCs, encouraging them to differentiate into nerve cells and quickly regenerate damaged axons. In rats with SCI, the DH significantly improved motor skills, as seen in better locomotor scores and muscle action potentials, showing a return of functional movement. This suggests nanoscale chirality-dependent metabolic reprogramming of NSCs could be a valuable approach in regenerative medicine.

Study Duration

8 Weeks

Participants

Sprague−Dawley rats

Evidence Level

Not specified

Key Findings

1
Dextral hydrogel (DH) promotes neural differentiation of NSCs and improves neural regeneration in rat SCI models by regulating fatty acid metabolism of NSCs.
2
DH enhances the production of growth factors, including IGF-1, VEGF, BDNF, NGF and stimulates the production of PGE2 by NSCs.
3
DH significantly increased the neuronal differentiation of NSCs, as indicated by a more significant number of BrdU+/MAP2+ cells than in the LH and control groups.

Research Summary

This study introduces a novel method using a chiral nanofiber-based extracellular matrix (ECM) to metabolically reprogram neural stem cells (NSCs) for spinal cord injury (SCI) treatment. The dextral nanofiber-hydrogel (DH) specifically reprograms lipid metabolism in NSCs, promoting neural differentiation and axon regeneration. The underlying mechanism involves the stereoselective interaction between DH and fatty acid-binding protein 5 (FABP5), enhancing fatty acid oxidation (FAO) and sphingosine biosynthesis. In a rat SCI model, DH significantly improved locomotor scores and muscle action potentials, indicating functional recovery. The findings demonstrate that nanoscale chirality-dependent metabolic reprogramming of NSCs offers new insights into stem cell physiology and regenerative medicine, suggesting potential applications beyond SCI treatment in various neurological disorders.

Practical Implications

Therapeutic Development

The use of chiral biomaterials can be further explored for targeted metabolic reprogramming of stem cells in regenerative therapies.

Drug Delivery

Chiral hydrogels can be utilized as drug delivery systems to enhance the efficacy of neuroprotective agents for SCI.

Personalized Medicine

Understanding the stereoselective interactions between chiral materials and cellular components can lead to personalized treatments tailored to individual patient needs.

Study Limitations

1
The precise long-term effects of DH on NSC differentiation and integration in the spinal cord need further investigation.
2
The study focuses primarily on lipid metabolism; other metabolic pathways influenced by chirality require further exploration.
3
The rat SCI model may not fully represent the complexities of human SCI, limiting the direct translatability of the findings.

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