Transplantation of hUC-MSCs seeded collagen scaffolds reduces scar formation and promotes functional recovery in canines with chronic spinal cord injury

Abstract

Spinal cord injury (SCI) can lead to locomotor deficits, and the repair of chronic SCI is considered one of the most challenging clinical problems. Although extensive studies have evaluated treatments for acute SCI in small animals, comparatively fewer studies have been conducted on large-animal SCI in the chronic phase, which is more clinically relevant. Here, we used a collagen-based biomaterial, named the NeuroRegen scaffold, loaded with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a canine chronic SCI model. To generate chronic SCI, the T8 spinal cord segment was removed by complete transection of the spinal cord. Two months later, glial scar tissue was removed and a NeuroRegen scaffold was transplanted into the lesion area. Functionalized NeuroRegen scaffold implantation promoted both locomotor recovery and endogenous neurogenesis in the lesion area. Moreover, some newly generated neurons successfully matured into 5-HT-positive neurons at 1 year post-injury. In addition, many regenerated axon fibers in the lesion area exhibited remyelination and synapse formation at 1 year post-injury in the functionalized NeuroRegen scaffold group. In conclusion, the NeuroRegen scaffold functionalized with hUC-MSCs is a promising potential therapeutic approach to chronic SCI that promotes neuronal regeneration, reduces glial scar formation, and ultimately improves locomotor recovery.

Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair

“…We used hWJ‐MSCs, as these cells represent an easily accessible source, with high potential for clinical applications. Moreover, a therapeutic benefit of hWJ‐MSCs in SCI alone as well as in combination with a biomaterial has been shown previously in several experimental and clinical studies …”

“…Moreover, a therapeutic benefit of hWJ-MSCs in SCI alone as well as in combination with a biomaterial has been shown previously in several experimental and clinical studies. [35][36][37]…”

Repair of alveolar cleft bone defects by bone collagen particles combined with hUC-MSCs in rabbit

“…Compared with stem cells derived from bone marrow, stem cells derived from umbilical cord have the advantages of low immunogenicity, rapid proliferation, wide availability and no ethical concerns [19,20]. Chronic spinal cord injury to dogs has been treated with hUC-MSCs combined with collagen scaffolds [21].…”

Curcumin improves human umbilical cord derived mesenchymal stem cells survival and promotes motor outcome via ERK Signaling after spinal cord injury

“…Therefore, hUC-MSCs serve as preferential seed cells when compared with BMSCs. Researches have reported that the cell replacement therapy with hUC-MSCs improves locomotor outcomes after SCI in animal and preclinical studies [7][8][9] . The mechanism of hUC-MSCs reveal not only the differentiation into neural lineage cells to repair damaged tissues, but also on their capacity to provide a favorable environment for regeneration 10 .…”