ABSTRACT
INTRODUCTION: Fingolimod is the first confirmed oral immune-modulator to treat Relapsing-Remitting Multiple Sclerosis (RRMS). This study aimed to investigate the safety and efficacy of fingolimod therapy in Iranian patients with RRMS. METHODS: In our trial, 50 patients resistant to conventional interferon therapy were assigned to receive fingolimod 0.5 mg per day for 12 months. The number of Dadolinium (Gd)-enhanced lesions, enlarged T2 lesions, and relapses over 12 months were considered as endpoints and compared to baseline. Liver biochemical evaluations and lymphocyte count were done at baseline and in months 3, 6, and 12 of the study. Patients were also monitored for possible cardiovascular events within the first 24 h and other side effects routinely. RESULTS: Among the patients who completed the trial, the number of Gd-enhanced and enlarged T2 lesions over 12 months significantly decreased (P=0.03 and P<0.001, respectively). The proportion of relapse-free patients was higher compared to the onset of fingolimod administration. There were no significant alterations in the Expanded Disability Status Scale (EDSS) scores. A slight, transient increase was recorded in liver enzymes among the participants. Lymphocyte count reduced by 61% at month 1 and displayed a gradual increase until month 12. No bradycardia and macular edema were recorded. CONCLUSION: These findings indicate an effective first-line fingolimod therapy for the first time in Iranian patients with RRMS. The decrease in the number of new attacks and the amelioration of MRI lesions were the benefits of fingolimod therapy, suggesting that it is preferred to other medicines to treat RRMS in Iran.
ABSTRACT
Traumatic brain injury (TBI) can result in permanent brain function impairment due to the poor regenerative ability of neural tissue. Tissue engineering has appeared as a promising approach to promote nerve regeneration and to ameliorate brain damage. The present study was designed to investigate the effect of transplantation of the human meningioma stem-like cells (hMgSCs) seeded in a promising three-dimensional scaffold (RADA4GGSIKVAV; R-GSIK) on the functional recovery of the brain and neuroinflammatory responses following TBI in rats. After induction of TBI, hMgSCs seeded in R-GSIK was transplanted within the injury site and its effect was compared to several control groups. Application of hMgSCs with R-GSIK improved functional recovery after TBI. A significant higher number of hMgSCs was observed in the brain when transplanted with R-GSIK scaffold compared to the control groups. Application of hMgSCs seeded in R-GSIK significantly decreased the lesion volume, reactive gliosis, and apoptosis at the injury site. Furthermore, treatment with hMgSCs seeded in R-GSIK significantly inhibited the expression of Toll-like receptor 4 and its downstream signaling molecules, including interleukin-1ß and tumor necrosis factor. These data revealed the potential for hMgSCs seeded in R-GSIK to improve the functional recovery of the brain after TBI; possibly via amelioration of inflammatory responses. STATEMENT OF SIGNIFICANCE: Tissue engineered scaffolds that mimic the natural extracellular matrix of the brain may modulate stem cell fate and contribute to tissue repair following traumatic brain injury (TBI). Among several scaffolds, self-assembly peptide nanofiber scaffolds markedly promotes cellular behaviors, including cell survival and differentiation. We developed a novel three-dimensional scaffold (RADA16GGSIKVAV; R-GSIK). Transplantation of the human meningioma stem-like cells seeded in R-GSIK in an animal model of TBI significantly improved functional recovery of the brain, possibly via enhancement of stem cell survival as well as reduction of the lesion volume, inflammatory process, and reactive gliosis at the injury site. R-GSIK is a suitable microenvironment for human stem cells and could be a potential biomaterial for the reconstruction of the injured brain after TBI.
