Medical Student UC Davis School of Medicine Sacramento, California, United States
Disclosure(s):
Sirjan Mor, MS: No financial relationships to disclose
Introduction: Spinal cord injury (SCI) is a devasting disease with no effective cure. Placental mesenchymal stromal cells (PMSCs) and PMSC Extracellular vesicles (EVs) have unique neuroprotective, angiogenic, and antioxidant properties. For that reason, PMSCs are being used in the first-in-human clinical trial for fetal spina bifida. We hypothesized that these PMSCs and PMSC-EVs would provide a similar neuroprotective effect in SCI.
Methods: Sprague Dawley rats were given a right C5 hemi-contusion injury. Immediately after the injury, rats were treated with: Extracellular matrix (ECM) only (n=10), 1st trimester PMSCs seeded on ECM (n=13), 1st trimester PMSC-EVs seeded on ECM (n=9), 2nd trimester PMSCs seeded on ECM (n=10), and 2nd trimester PMSC-EVs seeded on ECM (n=8), and sham controls (n=8). Weekly motor function testing included Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale. After 8 weeks, rats were euthanized, and tissue collected for histology.
Results: IBB scoring showed that the rats that received 1st trimester PMSC-ECM (P=0.017), and 1st trimester EV-ECM (P=0.015) had significantly improved motor function of the ipsilateral forelimb compared to rats that were treated with ECM only. Additionally, 2nd trimester PMSC-ECM treatment group had a significant increase in motor function (P=0.014) compared to the group treated with ECM only. However, rats treated with 2nd trimester EV-ECM did not show a significant improvement in motor function compared to rats treated with ECM only (P=0.1275). Immunohistochemistry showed significantly increased axons in rats treated with 1st trimester PMSC-ECM (P=0.006) and 1st trimester EV-ECM (P=0.00004) compared to ECM only. Fewer reactive astrocytes were seen in 1st trimester PMSC and EV treated groups.
Conclusion : PMSCs and PMSC-EVs improved motor function recovery in a rodent model of SCI. 1st Trimester cells and EVs performed better than 2nd trimester cells and EVs. Reduced gliosis and increased neuron and axon counts suggest neuroprotective capabilities of both PMSC and cell-free EV treatment.
