Adipose-derived mesenchymal stem cells overexpressing prion improve outcomes via the NLRP3 inflammasome/DAMP signalling after spinal cord injury in rat

J Cell Mol Med, 2023 · DOI: 10.1111/jcmm.17620 · Published: January 1, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study investigates how modified stem cells can help after a spinal cord injury. They used stem cells from fat tissue and made them produce more of a protein called prion protein. The study found that these modified stem cells reduced inflammation and improved recovery in rats with spinal cord injuries. This happened because the cells affected certain pathways that cause inflammation. These modified stem cells, called PrPcOE-ADMSCs, appear to be more effective than regular stem cells in protecting the spinal cord after an injury.

Study Duration

42 days

Participants

32 adult male Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
PrPcOE-ADMSCs showed enhanced cellular viability, anti-oxidative stress, and migration capabilities compared to ADMSCs alone when exposed to H2O2 and lipopolysaccharide damages.
2
PrPcOE-ADMSCs significantly inhibited inflammatory patterns in Raw264.7 cells (macrophage cell line).
3
Rats treated with PrPcOE-ADMSCs showed significantly improved neurological functions compared to the SCI group, with better BBB scores from days 7-35.

Research Summary

This study investigates the therapeutic impact of PrPcOE-ADMSCs on protecting the integrity of the spinal cord against acute SCI in rodents and observed that the NLRP3 inflammasome and DAMP-inflammatory signalling pathways might play important roles in the damage of the spinal cord in the setting of SCI. PrPcOE-ADMSCs were better than ADMSCs merely in early improving the neurological function in rats after acute SCI. As compared with ADMSCs, the PrPcOE-ADMSCs owned a greater capacity to inhibit the inflammatory reaction and generation of oxidative stress, resulting in protecting the spinal cord against acute SCI.

Practical Implications

Enhanced Stem Cell Therapy

Overexpressing prion protein in ADMSCs enhances their therapeutic potential for spinal cord injury by improving cell viability and reducing inflammation.

Targeting Inflammatory Pathways

The NLRP3 inflammasome and DAMP-inflammatory signaling pathways are key targets for therapeutic intervention in spinal cord injury.

Clinical Translation

PrPcOE-ADMSCs could be considered for SCI patients, especially when they are refractory to conventional treatment, due to their superior ability to suppress inflammatory signaling.

Study Limitations

1
The study period of 42 days may not be long enough to define a true ‘chronic phase’ of SCI.
2
The study did not test whether two doses of cell therapy would be better than a single dose for improving the outcome in the setting of SCI.
3
The study did not utilize agonists or antagonists to prove or disprove the proposed signalling pathways of NLRP3 inflammasome and DAMP-inflammation involved in SCI.

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