Abstract
Owing to the antioxidant and anti-inflammatory functions of hemeoxygenase-1 (HO-1), HO-1-expressing canine adipose-derived mesenchymal stem cells (Ad-MSCs) could be efficacious in treating spinal cord injury (SCI). Further, frozen thawed HO-1 Ad-MSCs could be instantly available as an emergency treatment for SCI. We compared the effects of intravenous treatment with freshly cultured HO-1 Ad-MSCs (HO-1 MSCs), only green fluorescent protein-expressing Ad-MSCs (GFP MSCs), and frozen thawed HO-1 Ad-MSCs (FT-HO-1 MSCs) in dogs with acute SCI. For four weeks, dogs were evaluated for improvement in hind limb locomotion using a canine Basso Beattie Bresnahan (cBBB) score. Upon completion of the study, injured spinal cord segments were harvested and used for western blot and histopathological analyses. All cell types had migrated to the injured spinal cord segment. The group that received HO-1 MSCs showed significant improvement in the cBBB score within four weeks. This group also showed significantly higher expression of NF-M and reduced astrogliosis. There was reduced expression of proinflammatory cytokines (IL6, TNF-α, and IL-1β) and increased expression of anti-inflammatory markers (IL-10, HO-1) in the HO-1 MSC group. Histopathological assessment revealed decreased fibrosis at the epicenter of the lesion and increased myelination in the HO-1 MSC group. Together, these data suggest that HO-1 MSCs could improve hind limb function by increasing the anti-inflammatory reaction, leading to neural sparing. Further, we found similar results between GFP MSCs and FT-HO-1 MSCs, which suggest that FT-HO-1 MSCs could be used as an emergency treatment for SCI.
Highlights
A high dose of methylprednisolone sodium succinate (MPSS) is injected intravenously (IV) as an emergency treatment to induce antioxidation in dogs with acute spinal cord injury (SCI)
We evaluated whether IV injection of freshly cultured and frozen thawed HO-1overexpressed adipose-derived mesenchymal stromal cells (Ad-mesenchymal stem cells (MSCs)) is effective as an emergency treatment in dogs with acute SCI
HO-1 gene was successfully transfected into Ad-MSCs
Summary
A high dose of methylprednisolone sodium succinate (MPSS) is injected intravenously (IV) as an emergency treatment to induce antioxidation in dogs with acute spinal cord injury (SCI). A meta-analysis has demonstrated that there is no satisfactory improvement with the use of MPSS, and it is associated with adverse side effects such as severe gastrointestinal bleeding [1, 2]. A safer and more effective emergency treatment option is required. An alternative that has been attempted is IV administration of adipose-derived mesenchymal stromal cells (Ad-MSCs). Ad-MSCs and MPSS have different roles in controlling oxidative stress and inflammation in dogs with acute SCI [3]. Owing to the strong antioxidant and anti-inflammatory effects of hemeoxygenase-1 (HO-1), intraparenchymal injection of HO-1-expressing Ad-MSCs reduces inflammation and improves neuronal sparing in canine SCI compared to control Ad-MSCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
