Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury

Neural Regeneration Research, 2017 · DOI: 10.4103/1673-5374.205106 · Published: April 1, 2017

Spinal Cord Injury Genetics Research Methodology & Design

Simple Explanation

This study investigates how Mitomycin C (MMC), a drug known to reduce scarring, affects cells called fibroblasts that contribute to scar formation after spinal cord surgery. The researchers found that MMC can trigger a process called apoptosis (cell death) in these fibroblasts, potentially explaining how it reduces scar tissue. Further investigation revealed that this apoptosis involves a specific cellular stress pathway, the endoplasmic reticulum stress pathway, suggesting a target for further therapeutic interventions.

Study Duration

Not specified

Participants

Patients undergoing laminectomy; primary human epidural scar fibroblasts (HESFs)

Evidence Level

Not specified

Key Findings

1
MMC suppresses the growth of human epidural scar fibroblasts in a dose- and time-dependent manner.
2
MMC induces apoptosis in HESFs, and this process involves both death receptor and mitochondrial apoptotic pathways.
3
MMC induces endoplasmic reticulum stress in HESFs, contributing to apoptosis, as evidenced by increased expression of GRP78, CHOP, and caspase-4.

Research Summary

The study investigates the mechanism by which mitomycin C (MMC) reduces scar adhesion after surgical decompression for spinal cord injury, focusing on its effect on human epidural scar fibroblasts (HESFs). Results demonstrate that MMC inhibits HESF proliferation and induces apoptosis through both death receptor and mitochondrial pathways, with evidence pointing to the involvement of endoplasmic reticulum stress. The endoplasmic reticulum stress inhibitor salubrinal significantly inhibited MMC-induced cell viability loss and apoptosis, further supporting the role of this pathway in MMC's mechanism of action.

Practical Implications

Therapeutic Potential

Mitomycin C has potential as a therapeutic agent for preventing excessive postoperative scarring after surgical decompression in spinal cord injury patients.

Targeted Intervention

The endoplasmic reticulum stress pathway may be a target for future therapeutic interventions aimed at reducing epidural fibrosis.

Mechanism Clarification

Further research is needed to fully clarify the intracellular signal transduction mechanisms involved in MMC-induced apoptosis of HESFs.

Study Limitations

1
The intracellular signal transduction mechanisms remain to be clarified.
2
Study did not fully elucidate all apoptotic pathways involved in MMC-induced HESF apoptosis.
3
The IC50 was estimated at 10 μg/mL for the 24-hour incubation.

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