Improvement of Rat Spinal Cord Injury Following Lentiviral Vector-Transduced Neural Stem/Progenitor Cells Derived from Human Epileptic Brain Tissue Transplantation with a Self-assembling Peptide Scaffold

Abstract

Spinal cord injury (SCI) is a disabling neurological disorder that causes neural circuit dysfunction. Although various therapies have been applied to improve the neurological outcomes of SCI, little clinical progress has been achieved. Stem cell–based therapy aimed at restoring the lost cells and supporting micromilieu at the site of the injury has become a conceptually attractive option for tissue repair following SCI. Adult human neural stem/progenitor cells (hNS/PCs) were obtained from the epileptic human brain specimens. Induction of SCI was followed by the application of lentiviral vector-mediated green fluorescent protein–labeled hNS/PCs seeded in PuraMatrix peptide hydrogel (PM). The co-application of hNS/PCs and PM at the SCI injury site significantly enhanced cell survival and differentiation, reduced the lesion volume, and improved neurological functions compared to the control groups. Besides, the transplanted hNS/PCs seeded in PM revealed significantly higher migration abilities into the lesion site and the healthy host tissue as well as a greater differentiation into astrocytes and neurons in the vicinity of the lesion as well as in the host tissue. Our data suggest that the transplantation of hNS/PCs seeded in PM could be a promising approach to restore the damaged tissues and improve neurological functions after SCI.

Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats

“…In a previous study in which the combination of RADA16 and neural stem/progenitor cells was applied to the contused spinal cords of rats, the application of RADA16 without cells was found to also induce decreases in the lesion volume and functional recovery. 14 However, the amount of RADA16 hydrogel applied in their study was 10 times higher than that applied in our study (100 vs 10 µL, respectively), and no molecular analysis was performed. In another study, a mixture of RADA16 and SVVYGLR derived from osteopontin was applied to brain injury model zebrafish, but no functional recovery was observed after RADA16 application.…”

“…12 In recent studies on spinal cord regeneration, microvascular cells or neural stem/progenitor cells were transplanted with RADA16 into the contused spinal cords of rats, and RADA16 was found to attenuate inflammation and glial scar formation by inducing the neural differentiation of transplanted stem cells. 13,14 Modification of RADA16 with proangiogenic peptides, such as SVVYGLR derived from osteopontin, might enhance angiogenesis after central nervous system (CNS) lesions. 15 Notably, in our previous works, RADA16 modified with substance P showed a good therapeutic effect on hindlimb ischemia and promoted skin regeneration by acting as a good delivery system and recruiting intrinsic mesenchymal stem cells in various tissue defect models.…”

Comparison of the Regenerative Effect of Adipose Tissue Mesenchymal Stem Cell Encapsulated into Two Hydrogel Scaffolds on Spinal Cord Injury

“…The rats were kept in individual cages in a 12h light/dark cycle condition with free access to commercial food and tap water. SCI was induced using Precision Systems and Instrumentation, Lexington, according to the weight compression method (22). In brief, the rats were deeply anesthetized by intraperitoneal (IP) injection of ketamine and xylazine (80 and 10 mg/kg, respectively), and the dorsal skin was disinfected after shaving by ethanol 70% (v/v).…”

Cell Therapy for Neurological Disorders: The Perspective of Promising Cells

“…Brain-derived neurotrophic factor (BDNF)-overexpressing hNSPCs, glial cell line-derived neurotrophic factor (GDNF)-overexpressing hNSPCs, and insulin-like growth factor 1 (IGF-1)-overexpressing hNSPCs have all been shown significant therapeutic effects on neurological disorders [ 57 , 58 , 59 ]. In addition, pre-treating hNSPCs with a gamma-secretase inhibitor [ 60 ], metformin [ 61 ] or tumor necrosis factor α (TNFα) [ 62 ], co-transplantation of hNSPCs with MSCs [ 63 ] or using biomaterial scaffolds as a carrier for hNSPCs [ 64 , 65 ] have also been reported to improve their therapeutic potential for neurological diseases. However, it is worth noting that the subtype of hNSPCs may also influence their therapeutic effects for a specific disease.…”