The Long-Term Efficacy Study of Multiple Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cells Transplantations Combined With Surgery in Four Dogs With Lumbosacral Spinal Cord Injury

Abstract

Severe lumbosacral pain, paraparesis or paraplegia, and urinary incontinence are common but frustrating problems in dogs with lumbosacral spinal cord injury (SCI). The surgical interventions including stabilization and decompression may not restore satisfying neurological functions in severe SCI. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) show benefits in immunomodulation, anti-inflammation, and promotion of axonal growth and remyelination, and also display efficacy in several diseases in veterinary medicine. In this report, four dogs presented with fracture of sacrum vertebrae or fracture of seventh lumbar and lumbosacral displacement after road traffic accidents. The clinical signs include lumbosacral pain (4/4), paraparesis (3/4), paraplegia (1/4), and urinary incontinence (4/4). All dogs were treated by surgical decompression with or without stabilization 1 to 7 weeks after trauma. Allogeneic canine Ad-MSCs (cAd-MSCs) were injected locally on nerve roots through the surgical region in all dogs. One dose of intravenous transplantation and 4 doses of local transplantation were also performed within 8 weeks after the surgery separately. All dogs showed significant neurological improvements with normal ambulatory ability (4/4) and urinary control (3/4) 3 months after the surgery and the first cAd-MSCs transplantation. No side effect was related to multiple cAd-MSCs transplantations during 6 months monitoring in all dogs. In conclusion, multiple cAd-MSCs transplantations could be a recommended treatment combined with surgery in dogs with lumbosacral SCI.

Current Advances in Mesenchymal Stem Cell Therapies Applied to Wounds and Skin, Eye, and Neuromuscular Diseases in Companion Animals

“…The usual treatment in companion animals involves surgical stabilization or decompression, which includes the removal of diseased intervertebral disc material. However, recovery rates are variable and often unsatisfactory, failing to successfully restore neurological functions in the most severe cases [41]. Therefore, new therapeutic alternatives are required to reduce inflammation and promote tissue regeneration.…”

“…The characteristic anti-inflammatory and trophic activities of MSCs, along with their ability to stimulate axonal growth, remyelination, and cell proliferation, could be a stimulus for the regeneration process in damaged tissues [41,42]. However, to date, the results obtained in different studies display considerable variability due to several reasons.…”

“…To date, only one study in dogs with SCI included up to six administrations, with no adverse effects during the 6-month follow-up [41]. In this research, four dogs with SCI resulting from traffic accidents, with previous surgical decompression, were treated with a first dose of 5 × 10 6 allogeneic ad-MSCs to the nerve roots at the site of the injury plus another IV dose of 4 × 10 6 cells/kg of weight, administered 30 min after surgery.…”

Beyond Canine Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells Transplantation: An Update on Their Secretome Characterization and Applications

“…One key area needing investigation is the development of methods for enhancing the intrinsic regenerative capacity of injured axons [76]. Indeed, the transplantation of AT-MSCs in various SCI animal models has shown beneficial effects on immunomodulation, inflammation, and the promotion of re-myelination and axonal growth [77][78][79][80].…”

Implantation of adipose-derived mesenchymal stem cell sheets promotes axonal regeneration and restores bladder function after spinal cord injury

“…Stem cell transplantation is a promising approach to promote recovery of injuries or degenerative changes after SCI. Over the past two decades, several clinical and preclinical studies have reported that adipose-derived mesenchymal stem cells (ADSCs) have tremendous neuroprotective and regenerative potentials after SCI when delivered directly to the lesioned cavity that forms after injury [ 7 , 8 ]. Presently, ADSC injection and ADSC seeding in scaffold materials are the two most commonly used methods with the drawbacks of transplanted cell loss and death, and inflammatory reactions of the scaffolds, which limit their application in SCI repair [ 9 , 10 ].…”