Adult spinal cord tissue transplantation combined with local tacrolimus sustained-release collagen hydrogel promotes complete spinal cord injury repair

Cell Prolif., 2023 · DOI: 10.1111/cpr.13451 · Published: May 1, 2023

Spinal Cord Injury Immunology Biomedical

Simple Explanation

The study explores a new approach to spinal cord injury (SCI) repair using adult spinal cord tissue (aSCs) transplantation combined with a localized, sustained-release tacrolimus (Tac) collagen hydrogel (Col/Tac). This aims to improve graft survival while minimizing side effects. The Col/Tac hydrogel was designed to provide long-term, localized immunosuppression, reducing the need for systemic immunosuppressive drugs like Tac, which can cause severe side effects. The research found that Col/Tac hydrogel implantation improved the survival rate of SCI rats with aSC transplants, reduced immune rejection, promoted neurogenesis, and improved functional restoration compared to conventional Tac medication.

Study Duration

8 weeks

Participants

80 adult female Sprague–Dawley rats as recipients, and 60 adult green fluorescent protein (GFP)-expressing female transgenic Sprague–Dawley rats as donors.

Evidence Level

Not specified

Key Findings

1
The Col/Tac hydrogel exhibited suitable mechanical properties and long-term sustained Tac release behaviour.
2
Localized delivery of immunosuppressive agents by the Col/Tac hydrogel may be a promising strategy for overcoming immune rejection of transplants, with significant potential for clinical application in the future.
3
The Col/Tac hydrogel treatment enhanced the survival of aSC-transplanted SCI rats compared to the conventional Tac treatment.

Research Summary

This study developed a Col/Tac hydrogel for localized delivery of immunosuppressive agents to improve the repair effects of transplanted aSC by immune regulation and reduction of Tac side effects. The Col/Tac hydrogel was shown to construct an immunosuppressive microenvironment after aSC transplantation to SCI recipients, improving graft survival and reducing transplant rejection, thereby improving functional recovery. Results indicated that co-implantation of aSC and Col/Tac hydrogel attenuated local immune rejection and promoted neural regeneration, thus enhanced therapeutic effects of the transplants and improving functional recovery in complete SCI rats.

Practical Implications

Clinical Translation

The collagen hydrogel-based immunosuppressive agent delivery system shows promise for improving the therapeutic efficiency of cell/tissue/organ transplantation in future clinical applications.

Reduced Systemic Toxicity

Localized Tac delivery reduces systemic toxicity and side effects of daily drug injection compared to conventional Tac medication.

Enhanced Graft Survival

The Col/Tac hydrogel enhances the survival of transplanted aSCs, which is critical for successful SCI repair.

Study Limitations

1
Long-term effects beyond 60 days were not extensively studied.
2
The study primarily used rat models, and results may not directly translate to human SCI.
3
Specific mechanisms of action for neuroprotection beyond immunosuppression require further investigation.

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