ABSTRACT
Objective: Amyotrophic lateral sclerosis [ALS] is the most severe disorder within the spectrum of motor neuron diseases [MND] that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous [IV] and intrathecal [IT] injections of bone marrow derived mesenchymal stromal cells [BM-MSCs] in patients with ALS
Materials and Methods: This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale [ALS-FRS] .24, and .40% predicted forced vital capacity [FVC]. All patients underwent bone marrow [BM] aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 [n=6] received an IV and patients in group 2 [n=8] received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging [MRI]. In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection
Results: During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups
Conclusion: This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible [Registration numbers: NCT01759797 and NCT01771640]
ABSTRACT
Wnt signaling pathway plays an important role in folliculogenesis of rodent ovaries; however, its involvement in ovarian apoptotic events remains undetermined. With respect to the importance of apoptosis in homeostasis and ovarian biological function, this experimental study was conducted to determine the effects of Wnt/ beta -catenin signaling on follicular growth arrest and apoptosis in polycystic ovary [PCO] models of rats. The experiments were performed in three independent series and with each set of experiments, 8 rats were allocated to the group, half of them as the controls and the other four as the testosterone propionate [TP]-treated rats for the indicated period of time [1 and 4 weeks]. Induction of PCO in immature rats was performed by daily injection of testosterone propionate [TP] dissolved in sesame oil over 1 and 4 weeks in the experimental group but to the control group solvent was injected. At the end of the experiments, the ovaries were fixed and sequential paraffin slices were prepared for immunohistochemical analyses of GSK3 beta, beta -catenin and pGSK3 beta ser9 proteins. Assessment of Sfrp4 expression as an antagonist of Wnt signaling pathway was performed by Western blot test. Analysis of apoptosis was done by TUNEL staining, followed by quantification of apoptotic follicles in the different groups. The data were analyzed by using Mann-Whitney U-test and a p-value <0.05 was considered significant. Histological analysis of TP-treated rats showed cystic follicles, absence of corpus luteum and anovulation. GSK3 beta expression in apoptotic follicles of PCO-induced and control groups was observed. In addition, co-localization of nuclear beta -catenin and pGSK3 beta ser9 in 1-week-treated rats was detected. In long-term TP-treated rats, there was an increase in apoptosis and GSK3 beta expression and a 5.1 fold increase in Sfrp4 expression in granulosa cells, compared with the control group, which may explain the absence of nuclear beta -catenin in these cells. The results show testosterone propionate injections induces PCO in immature rats. in long-term treatment Furthermore, the increased expression of Sfrp4 and GSK3 beta with TP was associated with apoptosis. These results may reveal Wnt signaling inhibition in apoptotic events of rodent ovaries