Interleukin‑10 genetically modified clinical‑grade mesenchymal stromal cells markedly reinforced functional recovery after spinal cord injury via directing alternative activation of macrophages

Cellular & Molecular Biology Letters, 2022 · DOI: https://doi.org/10.1186/s11658-022-00325-9 · Published: March 14, 2022

Spinal Cord Injury Regenerative Medicine Immunology

Simple Explanation

This study explores the therapeutic potential of interleukin-10 (IL10) genetically modified mesenchymal stromal cells (IL10-MSCs) in a mouse model of completely transected spinal cord injury (SCI). The research aims to assess their clinical safety, effectiveness, and mechanism of action. The researchers established stable IL10-overexpressing human umbilical-cord-derived MSCs and administered them to SCI mice via tail intravenous injections. They then examined motor function, histological structure, and nerve regeneration. The results showed that IL10-MSC treatment significantly improved locomotor function, reduced lesion size, promoted axon regeneration, and preserved neurons compared to unmodified MSCs. The treatment also increased the ratio of M2 macrophages and reduced the ratio of M1 macrophages at the injury site.

Study Duration

Not specified

Participants

56 adult female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
IL10-MSC treatment markedly reinforced locomotor improvement, accompanied with decreased lesion volume, regeneration of axons, and preservation of neurons, compared with naïve unmodified MSCs.
2
IL10-MSC transplantation increased the ratio of microglia to infiltrated alternatively activated macrophages (M2), and reduced the ratio of classically activated macrophages (M1) at the injured spinal cord.
3
IL10-MSCs exhibited a reliable safety profile and demonstrated promising therapeutic efficacy in SCI compared with naïve MSCs, providing solid support for future clinical application of genetically engineered MSCs.

Research Summary

The study investigates the therapeutic potential of IL10-modified MSCs in a mouse model of SCI. IL10-MSCs were generated and assessed for safety and efficacy, showing improved motor function recovery and reduced lesion size compared to unmodified MSCs. The mechanism of action involves promoting M2 macrophage polarization at the injury site and modulating the peripheral immune system. IL10-MSCs also demonstrated the ability to rescue neuronal differentiation and survival of neural stem cells in an inflammatory environment in vitro. The research provides evidence supporting the clinical application of IL10-modified MSCs for SCI treatment, emphasizing the importance of systematic quality and safety evaluations for gene-modified cell therapies.

Practical Implications

Clinical Translation

Provides a foundation for future clinical trials using IL10-MSCs for spinal cord injury treatment, given their demonstrated safety profile and therapeutic efficacy in preclinical studies.

Therapeutic Strategy

Supports the use of genetically modified MSCs as a viable strategy for enhancing therapeutic outcomes in SCI, particularly by modulating the immune response and promoting tissue repair.

Quality Control

Highlights the necessity of rigorous quality assessment and safety evaluations for gene-modified cell-based therapies to ensure their safe and effective clinical application.

Study Limitations

1
The study is limited to a mouse model, and results may not directly translate to human patients.
2
Further research is needed to optimize the dosage and administration route of IL10-MSCs for clinical use.
3
Long-term effects and potential side effects of IL10-MSC therapy require further investigation.

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