Autologous exosome facilitates load and target delivery of bioactive peptides to repair spinal cord injury

Bioactive Materials, 2023 · DOI: https://doi.org/10.1016/j.bioactmat.2022.07.002 · Published: January 1, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injury (SCI) leads to motor, sensory, and automatic impairment due to limited axon regeneration. An effective non-invasive treatment strategy for SCI involves generating an autologous plasma exosome (AP-EXO) based biological scaffold. This scaffold is loaded with neuron targeting peptide (RVG) and growth-facilitating peptides (ILP and ISP) to target the injured area and promote motor functional recovery. The AP-EXO-based personalized treatment facilitates functional recovery after SCI and holds immense promise in biomedical applications. It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes. The functional recovery is achieved by inhibiting inflammatory response, stimulating robust axon regrowth, and promoting new intraspinal circuit formation. This study demonstrates a novel non-invasive biological repair strategy with a peptide-loaded exosome preparation. It augments motor functional recovery and offers important insights into the clinical translation of exosomes loaded with three bioactive peptides in treating SCI. The AP-EXO-based scaffold exhibits high efficacy for treating SCI as the AP-EXO and peptides are coordinate and compensate each other.

Study Duration

5 weeks

Participants

C57BL/6 mice and BALB/c nude mice

Evidence Level

Not specified

Key Findings

1
AP-EXOR&L&S enables its homing competency to SCI injury sites where multifunctional peptide-loaded AP-EXO exerted their potential effect on SCI repair by directly targeting the lesion sites.
2
AP-EXOR&L&S enables axon regeneration and motor function recovery after spinal cord contusion in SCI mice evidenced by BMS scores and gait analysis.
3
HP-EXOR&L&S elicits functional recovery following SCI without triggering any detectable toxicity and inflammation response.

Research Summary

This study developed an AP-EXO-based biological scaffold by anchoring neuron-targeting and growth-facilitating peptides, improving the targeting specificity and therapeutic efficacy of bioactive peptides for SCI treatment. The AP-EXO scaffold offers advantages like non-secondary injury to the spinal cord, non-immunogenicity, and enhanced therapeutic benefits, leading to robust axon regeneration and new intraspinal circuit formation. The research validated the effectiveness and safety of exosomes from healthy human plasma (HP-EXO) as peptide delivery vehicles, showing similar positive effects as AP-EXOR&L&S in SCI models of nude mice without adverse effects.

Practical Implications

Clinical Translation

The AP-EXO-based scaffold can be translated into clinical applications as a personalized treatment for SCI due to its safety and efficacy.

Targeted Drug Delivery

The AP-EXO delivery system can be applied to deliver other therapeutic cargos to specific cells in the injured spinal cord, maximizing their therapeutic effects.

Personalized Medicine

The use of autogenously derived exosomes provides vital clues in personalized treatment scheme for SCI recovery.

Study Limitations

1
The study does not fully elucidate which individual peptide in the AP-EXOR&L&S mixture primarily contributes to the therapeutic outcomes.
2
Further studies are needed to explore the underlying molecular mechanisms of neural regeneration and functional recovery in detail.
3
Efficacy and safety of AP- EXOR&L&S need to be validated in large animal models.

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