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

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Neuroscience

Background:

• Exogenous neural stem cells (NSCs) offer potential for spinal neural circuitry repair.
• Controlling NSC metabolic reprogramming for effective nerve regeneration remains a challenge.
• Lipid metabolism plays a crucial role in neural differentiation and axon growth.

Purpose of the Study:

• To investigate the effect of a biomimetic dextral hydrogel (DH) on NSC metabolic reprogramming.
• To explore the potential of DH in promoting neural differentiation and spinal cord regeneration.
• To elucidate the mechanism underlying DH-mediated NSC metabolic modulation.

Main Methods:

• Fabrication of a dextral hydrogel (DH) with right-handed nanofibers.
• Assessment of DH's effect on NSC lipid metabolism, including fatty acid oxidation (FAO) and sphingosine biosynthesis.
• Evaluation of DH efficacy in a rat spinal cord injury (SCI) model, measuring locomotor recovery (BBB scores) and nerve function (compound muscle action potential).

Main Results:

• DH specifically reprograms NSC lipid metabolism through stereoselective interaction with fatty acid-binding protein 5 (FABP5).
• DH enhances FAO and sphingosine biosynthesis, promoting NSC neural differentiation and axon regeneration.
• In the rat SCI model, DH significantly improved locomotor function (BBB scores >3-fold) and hindlimb motor evoked potentials (>4-fold).

Conclusions:

• Nanoscale chirality of DH can effectively reprogram NSC metabolism for enhanced nerve regeneration.
• DH-mediated metabolic reprogramming offers a promising strategy for treating spinal cord injuries.
• This study provides insights into stem cell physiology and opens new avenues for regenerative medicine.