Exploring the potential of induced neural stem cells (iNSCs) as therapy for spinal cord injury in a rat model

Spinal cord injury (SCI) is a severe condition associated with high morbidity and mortality rates. As of now, no effective therapies are available. However, induced neural stem cells (iNSCs) offer a promising therapeutic approach by enabling autologous transplantation.In the subchronic phase 30 days post-SCI, we conducted the transplantation of fGFP-labelled human iNSCs (or vehicle) into female Fischer-344 rats with moderate to severe spinal cord injuries at the T8 level. One day prior to cell transplantation, immunosuppressive treatment was started and maintained to prevent graft rejection throughout the observational period. Motor and sensory functions were assessed using the BBB locomotor scale, Catwalk XT system, and Hargreaves test.Immunohistochemistry one month post-transplantation revealed engraftment of iNSCs, observed both as cell clusters with frequent expression of Ki67 (indicating proliferation) and hNestin (marker of neural stem cell), as well as single cells expressing early neuronal markers such as Doublecortin (DCX) and beta-III-tubulin. These findings suggest ongoing neuronal differentiation. The astrocytic marker glial fibrillary acidic protein (GFAP) was not observed at this time point. In contrast, three months post-transplantation, iNSCs exclusively exhibit GFAP expression, while DCX and beta-III-tubulin expression was absent. iNSCs transplantation did neither improve nor aggravate motor or sensory functions.In future studies, we will modulate the microenvironment to augment iNSC trophic support, neuronal differentiation, survival and integration. Despite the absence of significant functional improvement in this study, iNSC transplantation remains a safe approach with potential for future spinal cord injury treatment.