Collagen/heparin sulfate scaffold combined with mesenchymal stem cells treatment for canines with spinal cord injury: A pilot feasibility study

Abstract

Background: Due to endogenous neuronal deficiency and glial scar formation, spinal cord injury (SCI) often leads to irreversible neurological loss. Accumulating evidence has shown that a suitable scaffold has important value for promoting nerve regeneration after SCI. Collagen/heparin sulfate scaffold (CHSS) has shown effect for guiding axonal regeneration and decreasing glial scar deposition after SCI. The current research aimed to evaluate the utility of the CHSSs adsorbed with mesenchymal stem cells (MSCs) on nerve regeneration, and functional recovery after acute complete SCI. Methods: CHSSs were prepared, and evaluated for biocompatibility. The CHSSs adsorbed with MSCs were transplanted into these canines with complete SCI. Results: We observed that MSCs had good biocompatibility with CHSSs. In complete transverse SCI models, the implantation of CHSS co-cultured with MSCs exhibited significant improvement in locomotion, motor evoked potential, magnetic resonance imaging, diffusion tensor imaging, and urodynamic parameters. Meanwhile, nerve fibers were markedly improved in the CHSS adsorbed with MSCs group. Moreover, we observed that the implantation of CHSS combined with MSCs modulated inflammatory cytokine levels. Conclusions: The results preliminarily demonstrated that the transplantation of MSCs on a CHSS could improve the recovery of motor function after SCI. Thus, implanting the MSCs-laden CHSS is a promising combinatorial therapy for treatment in acute SCI.

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

“…Furthermore, some experimental studies in canine models of SCI included MSCs within polymeric structures or scaffolds that are implanted at the site of the injury, resulting in significant advances in the regeneration of damaged tissue. Thus far, the material of these scaffolds used together with MSCs is variable, i.e., poly lactic-glycolic acid [67], matrigel [25,68], collagen/sulfate of heparin [69], or linear collagen [70], showing significant improvements in hindlimb locomotor recovery, neural regeneration, good integration into host tissue, and reduced fibrosis.…”

Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review

“…Its high biocompatibility, hydrophilic nature, abundance in somatic tissues, and high degree of cellular adhesion allows it to be synthesized into scaffolds [106]. Consequently, collagen-derived stem cell scaffolds for SCI have been studied extensively throughout the literature (Table 1) [128][129][130][131][132][133][134][135]. Specifically, collagen-based stem cell scaffolds recruit and protect embryonic neural stem progenitor cells (NSPCs) at SCI lesions, promote neural stem cell (NSC) adhesion, proliferation, and differentiation, and improve locomotor behaviors in murine models [128,129].…”

“…When transplanted into rats with complete spinal cord tran-sections, the N-cadherin-modified collagen scaffold recruited more NSPCs to the lesion site and consequently, LOCS-Ncad rats demonstrated significantly improved locomotor function as compared to controls [128]. Similarly, collagen scaffolds seeded with MSCs can be further enhanced by the addition of silk fibroin or heparan sulfate [132,133,135]. Silk fibroin is a natural fibrous protein found in silk and spider webs.…”

Can a Scaffold Enriched with Mesenchymal Stem Cells Be a Good Treatment for Spinal Cord Injury?

“…These tests were carried out because urination is an essential outcome in the assessment of neurological recovery. The levels of IL-1β and TNF-α were suppressed after 7 and 14 days, while the levels of IL-10 and TGF-β1 significantly increased, indicating that the transplantation could upregulate the expression of anti-inflammatory factors and downregulate the expression of pro-inflammatory factors [ 79 ]. One study that confirms the Deng et al studies of neurogenesis in acute SCI is that of Zou et al They used a longitudinal collagen sponge scaffold enriched with hUC-MSCs (density of 2 × 10 6 cells) grafted immediately after the completely transected spinal cord in rats.…”