Effects of Combinatorial Treatment with Pituitary Adenylate Cyclase Activating Peptide and Human Mesenchymal Stem Cells on Spinal Cord Tissue Repair

This study investigates whether combining human mesenchymal stem cells (hMSCs) and pituitary adenylate cyclase-activating polypeptide (PACAP) can improve recovery from severe spinal cord injury (SCI) in rats. The researchers used modified hMSCs that can develop into nerve cells and produce beneficial growth factors. The findings showed that delayed treatment with both PACAP and hMSCs, started a week after the injury, helped preserve nerve fibers in the damaged spinal cord. This combined treatment led to better movement recovery in the rats compared to using PACAP or hMSCs alone. Further experiments revealed that the combined treatment increased antioxidant enzyme levels in the injured area and enhanced the ability of certain brain cells (astrocytes) to remove excess glutamate, a substance that can be harmful in high concentrations.

• 1
  Delayed treatment with PACAP and hMSCs at day 7 post SCI increased the remaining neuronal fibers in the injured spinal cord, leading to better locomotor functional recovery in SCI rats when compared to treatment only with PACAP or hMSCs.
• 2
  The levels of antioxidant enzymes, Mn-superoxide dismutase (MnSOD) and peroxiredoxin-1/6 (Prx-1 and Prx-6), were increased at the lesion center 1 week after the delayed treatment with the combinatorial therapy when compared to that observed in the vehicle-treated control.
• 3
  Co-culture with hMSCs in the presence of PACAP not only increased a subpopulation of microglia expressing galectin-3, but also enhanced the ability of astrocytes to uptake extracellular glutamate.