Experimental autoimmune encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS) is characterized by demyelination, infiltration of inflammatory cells into the nervous system and dysregulation of serum inflammatory cytokines. We investigated the correlation of serum cytokines and other inflammatory markers with the EAE pathogenesis. After EAE induction, the levels of different serum cytokine/inflammatory mediators were measured. Furthermore, motor functions, myelination, and lymphocyte infiltration in EAE mice were also assessed. Our results revealed that the serum concentrations of Thelper 1 (Th1) and Th17 cytokines, interleukin (IL)-6, IL-1β, IL-1α and prostaglandin E2 in EAE mice were significantly higher than controls. The ratios of pro-to anti-inflammatory cytokines were different between the EAE and the control group. A statistically significant positive correlation was found between the IL-6/IL-10 ratio and the EAE severity, demyelination rate, and lymphocyte infiltration in EAE mice. Results indicate that the profiles of serum pro-and anti-inflammatory cytokines might be useful as biomarkers for monitoring the pathological manifestation of EAE. Furthermore, evaluating the dynamic interplay of serum cytokine levels and the correlation with pathogenic mechanisms of EAE may provide diagnostic and therapeutic insights for MS and some other inflammatory disorders.
Traumatic brain injury (TBI) is a disruption in the brain functions following a head trauma. Cell therapy may provide a promising treatment for TBI. Among different cell types, human neural stem cells cultured in self-assembling peptide scaffolds have been suggested as a potential novel method for cell replacement treatment after TBI. In the present study, we accessed the effects of human neural stem/progenitor cells (hNS/PCs) derived from epileptic human brain and human adipose-derived stromal/stem cells (hADSCs) seeded in PuraMatrix hydrogel (PM) on brain function after TBI in an animal model of brain injury. hNS/PCs were isolated from patients with medically intractable epilepsy undergone epilepsy surgery. hNS/PCs and hADSCs have the potential for proliferation and differentiation into both neuronal and glial lineages. Assessment of the growth characteristics of hNS/PCs and hADSCs revealed that the hNS/PCs doubling time was significantly longer and the growth rate was lower than hADSCs. Transplantation of hNS/PCs and hADSCs seeded in PM improved functional recovery, decreased lesion volume, inhibited neuroinflammation, and reduced the reactive gliosis at the injury site. The data suggest the transplantation of hNS/PCs or hADSCs cultured in PM as a promising treatment option for cell replacement therapy in TBI.
Considerable efforts have been made to combine biologically active molecules into the self-assembling peptide in order to improve cells growth, survival, and differentiation. In this study, a novel three-dimensional scaffold (RADAGGSIKVAV; R-GSIK) was designed by adding glycine and serine between RADA4 and IKVAV to promote the strength of the peptide. The cell adhesion, viability, proliferation, migration, and differentiation of rat embryonic neural stem cells (NSCs) in R-GSIK were investigated and compared to laminin-coated, two-dimensional, and Puramatrix cultures. The scanning electron microscopy studies of the R-GSIK showed an open porous structure and a suitable surface area available for cell interaction. R-GSIK promoted the cell adhesion, viability, proliferation, and migration compared to the other cultures. In addition, the R-GSIK enhanced NSCs differentiation into neuronal cells. The NSCs injected in R-GSIK had a lower glial differentiation rate than in the Puramatrix. The results suggest that R-GSIK holds great promise for cell therapies and neuronal tissue repair.
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