Epidermal neural crest stem cell‐derived glia enhance neurotrophic elements in an ex vivo model of spinal cord injury

Abstract

Growing evidence that cell-based therapies can improve recovery outcome in spinal cord injury (SCI) models substantiates their application for treatment of human with SCI. To address the effectiveness of these stem cells, potential candidates should be evaluated in proper SCI platform that allows direct real-time monitoring. In this study, the role of epidermal neural crest stem cells (EPI-NCSCs) was elucidated in an ex vivo model of SCI, and valproic acid (VPA) was administered to ameliorate the inhospitable context of injury for grafted EPI-NCSCs. Here the contusion was induced in organotypic spinal cord slice culture at day seven in vitro using a weight drop device and one hour post injury the GFP- expressing EPI-NCSCs were grafted followed by VPA administration. The evaluation of treated slices seven days after injury revealed that grafted stem cells survived on the injured slices and expressed GFAP, whereas they did not express any detectable levels of the neural progenitor marker doublecortin (DCX), which was expressed prior to transplantation. Immunoblotting data demonstrated that the expression of GFAP, BDNF, neurotrophin-3 (NT3), and Bcl2 increased significantly in stem cell treated slices. This study illustrated that the fate of transplanted stem cells has been directed to the glial lineage in the ex vivo context of injury and EPI-NCSCs may ameliorate the SCI condition through releasing neurotrophic factors directly and/or via inducing resident spinal cord cells.

Neural crest-like stem cells for tissue regeneration

“…Axon regeneration does not occur due to the nonresponsive environment of the injured spinal cord. Emerging evidence suggests that NCLSCs derived from various adult tissues may serve a promising strategy for SCI 111‐113 . Recently, human dental pulp (hDP)‐NCSCs were used to evaluate the effect of hDP‐NCSC delivery on the lesion site and functional recovery after SCI 111 .…”

Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair

“…While not essential to demonstrate the biocompatibility of hydrogels in our model, inclusion of these groups would be ideal to better mimic the in vivo environment where the neural tube defect remains in contact with amniotic fluid. 88,89 Such studies may also allow us to assess neural inflammation and the role of microglia during tissue regeneration. Finally, findings within this small animal model may be species-specific and therefore would likely require subsequent validation in scale-up studies on human tissues prior to clinical translation.…”

Human Dental Pulp Stem Cells Display a Potential for Modeling Alzheimer Disease-Related Tau Modifications

“…As neurons produced from these stem cells lacked tau protein, they can be of utility in regenerative medicine but not in modeling tau-related aspects of neurodegeneration. In contrast, DPSCs are known from embryological (61) studies to stem from ectodermal-neuroepithelial-neural crest lineage producing, among many cell types, cells of the peripheral neural system and glia (62,63).…”