A functionalized self-assembling peptide containing E7 and YIGSR sequences enhances neuronal differentiation of spermatogonial stem cells on aligned PCL fibers for spinal cord injury repair

Theranostics, 2022 · DOI: 10.7150/thno.78448 · Published: October 31, 2022

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

Spinal cord injuries (SCI) lead to nerve cell death and disrupt nerve fibers, causing loss of movement and sensation. A promising treatment involves transplanting new neurons grown from stem cells into the injured area. This study uses spermatogonial stem cells (SSCs) that can become like embryonic stem cells and turn into specific types of neurons. The challenge is to make this process more efficient. Researchers created a special coating with the Nap-E7-YIGSR peptide on aligned PCL fibers to help SSCs turn into neurons. The results showed better nerve regeneration and motor function recovery in rats with spinal cord injuries.

Study Duration

7 weeks

Participants

SD rats

Evidence Level

Not specified

Key Findings

1
The Nap-E7-YIGSR peptide enhances the adhesion of SSCs to PCL fibers, improving the material's hydrophilicity and SSC affinity.
2
Nap-E7-YIGSR effectively induces SSC neuron differentiation by activating the integrin β1/GSK3β/β-catenin signaling pathway.
3
SSCs-derived neurons implanted into SCI lesion sites in rats resulted in new relay circuits, myelination, synapse formation and improved locomotion.

Research Summary

This study introduces a novel self-assembled peptide, Nap-E7-YIGSR, coated on aligned PCL fibers, designed to enhance neuronal differentiation of spermatogonial stem cells (SSCs) for spinal cord injury (SCI) repair. In vitro experiments demonstrated that Nap-E7-YIGSR improves SSC adhesion, proliferation, and differentiation into neurons by activating the integrin β1/GSK3β/β-catenin signaling pathway. In vivo studies using a rat SCI model showed that transplantation of SSC-derived neurons led to neural circuit reconstruction, improved motor function, reduced muscle atrophy, and decreased glial scar formation.

Practical Implications

Improved SCI Treatment

The multifunctional peptide and aligned fibers may trigger SSC differentiation to neurons, which would facilitate neuronal replacement therapy and promote functional recovery after SCI.

CNS Regenerative Medicine

This multi-domain self-assembling peptide strategy may be a powerful tool for neuronal differentiation of stem cells and neuronal replacement in CNS regenerative medicine.

Drug Delivery Systems

The self-assembling peptide approach can be adapted for targeted drug delivery to enhance therapeutic outcomes in various disease models.

Study Limitations

1
The specific types of neurons differentiated from SSCs and their distinct therapeutic activities require further investigation.
2
The long-term effects and potential complications of transplanting SSC-derived neurons need to be thoroughly evaluated.
3
The study primarily focused on a rat model of SCI, and further research is needed to translate these findings to human clinical trials.

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