Therapeutic Efficacy of Mesenchymal Stem Cells and Mesenchymal Stem Cells-derived Neural Progenitors in Experimental Autoimmune Encephalomyelitis.

BACKGROUND AND OBJECTIVES: The goal of treatment for MS is to reduce the inflammation and induce the regeneration of degenerated axons. Considering the anti-inflammatory and regenerative capacity of mesenchymal stem cell (MSCs), in this study the therapeutic efficacy of allogeneic MSCs and MSCs-derived neural progenitor cells (MSCs-NPs) was investigated in cellular therapy of chronic experimental autoimmune encephalomyelitis (EAE). METHODS AND RESULTS: MSCs, MSCs-NPs and MSCs＋MSCs-NP were administered intravenously to EAE mice on days 22, 29, and 36 post immunization. The levels of cytokines and PGE2 in sera or supernatant of in vitro cultured splenocytes derived from treated mice were measured by ELISA. The results of this study showed that in comparison to MSCs monotherapy, MSCs-NPs administration had a more profound capability of inhibiting the proliferation of pathogenic MOG35₋55-specific T cells, decreasing IFN-γ production and increasing anti-inflammatory IL-10 cytokine production. These findings could be explained by higher ability of in vitro cultured MSCs-NPs in production of PGE2 compared to MSCs. In line with these findings, while the administration of MSCs and MSCs-NPs significantly decreased the clinical scores of EAE in comparison with the untreated EAE group, MSCs-NPs were significantly more efficient in reducing clinical score compared to MSCs. Of interest, combined therapy with MSCs and MSCs-NPs did not provide any benefit over monotherapy with MSCs-NPs. CONCLUSIONS: In comparison to MSCs, allogenic MSCs-NPs are more potent in the attenuation of EAE.

Evaluation of serum interleukin- 35 level in children with persistent asthma.

BACKGROUND: IL-35 is a novel cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development. Few studies have been done on the effect of this cytokine in a different disease. Asthma is a complex disease that many inflammatory cells and cytokines play a role in. OBJECTIVE: We decide to determine the difference between serum level of IL-35 in childhood asthma & healthy children. METHOD: We obtained serum samples from 44 asthmatic children between 2 and 15 years as a case group and from healthy children as a control group. IL-35 serum concentration was determined by ELISA method in both groups. RESULTS: Mean serum level is 30.9 pg/ml in the case group and 30.2 pg/ml in the control group. There is no significant difference between serum level of IL-35 in asthmatic & healthy children. CONCLUSIONS: Our data reveal no relation between childhood asthma and serum level of IL35. So, further study will be needed to clarify effects of this cytokine in human allergic diseases.

Engraftment of plasma membrane vesicles into liposomes: A new method for designing of liposome-based vaccines.

OBJECTIVES: One of the major challenges in the field of vaccine design is choosing immunogenic antigens which can induce a proper immune response against complex targets like malignant cells or recondite diseases caused by protozoan parasites such as leishmaniasis. The aim of this study was to find a way to construct artificial liposome-based cells containing fragments of target's cell membrane. This structure not only mimics the real biological properties of proteins in the cell membrane of target cells, but also may induce the required immune responses, which culminate in eradication of target cells. MATERIALS AND METHODS: Five different techniques have been investigated to engraft the plasma membrane's vesicles (PMVs) derived from a characterized Leishmania parasite into liposomes. The most efficient method was tested again on the PMVs derived from well-known breast cancer cell line SK-BR-3. The percentage of engraftment was determined by two-color flowcytometry after staining the engrafted dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine DiI-labeled liposomes with FITC-labeled PMVs. RESULTS: Among the investigated techniques, freeze-drying method with 91±2% and 90±3% of engraftment for Leishmania and SK-BR-3 derived PMVs, respectively, showed superiority over the other methods. In addition, after 9 weeks storage in refrigerator, freeze-dried fused particles kept their original size (660±350 nm) and fusion efficiency (94±3%). CONCLUSION: Among five different engraftment techniques, freeze-drying is preferred over the other methods due to its simplicity, more fusion efficiency and stability of produced particles during storage.

Association of IL-8 (-251 a/t) gene polymorphism with clinical parameters and chronic periodontitis.

OBJECTIVE: To investigate the correlation between IL-8 (-251 A/T) gene polymorphism and susceptibility to chronic periodontitis as well as different clinical parameters and severity of the condition in patients referred to dental school, Shiraz University of Medical Sciences, Shiraz, Iran. MATERIALS AND METHODS: In this randomized cross sectional study, 227 non-smoking patients with chronic periodontitis (test) and 40 healthy individuals (control) were enrolled in this experiment and the following clinical parameters were employed in the study: Periodontal Pocket Depth (PPD), Clinical Attachment Level (CAL) and Bone Loss (BL). All participants underwent the PCR (Polymerase Chain Reaction) test to detect 251 A/T Single Nucleotide Polymorphism of IL8 gene. RESULTS: No significant correlation was perceived between different genotypes of IL-8 and the severity of the periodontal condition (P= 0.164), neither did we detect any substantial association between different IL-8 genotypes and the mean PPD (P=0.525), CAL (P=0.151), BL (P=0.255), PI (P=0.087), BOP (P=0.265) and the average number of teeth (P=0.931). CONCLUSION: The results implied that there was no explicit correlation between 251 (A/T) IL-8 gene polymorphism and the severity of the chronic periodontal disease or to the susceptibility to it.

Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus.

Interleukin 6 (IL-6) has been shown to be related to the pathogenesis of systemic lupus erythematosus (SLE). In the present study, the relationship between two polymorphisms in the promoter region of IL-6 gene at positions -572 G/C and -174 G/C and disease susceptibility in 401 Iranian patients with SLE was investigated using polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution and allele frequencies of IL-6 gene polymorphism at -174 position showed no significant difference between SLE patients and controls. In contrary, both allelic and genotypic frequencies at the -572 position significantly differed in SLE patients and controls. At this position, GG genotype was observed in 77.9% of patients compared to 68.9% in the control group (p < 0.014). The frequency of -572 G allele in patients (87.3%) was also higher than in controls (83.2%; p = 0.034). The haplotype study showed no significant difference between patients and healthy subjects. Study of the relationship between these polymorphisms and clinical manifestations and laboratory parameters showed an association between -174 polymorphism and the presence of antinuclear antibodies in all patients and rash and hematuria in male patients (p < 0.04). At -572 polymorphism, a significant difference with regard to photosensitivity in male patients (p = 0.04) was found. In conclusion, results of this study showed that -572 polymorphism plays an important role in susceptibility to SLE and that -174 polymorphism could influence the presence of antinuclear antibodies in the patients.

Fas gene polymorphisms in systemic lupus erythematosus and serum levels of some apoptosis-related molecules.

The frequency of the Fas gene polymorphism at positions-1377 G/A and -670 A/G in 249 patients with systemic lupus erythematosus (SLE) and 212 healthy controls were investigated using the allele-specific polymerase chain reaction. On evaluation of genotype and allelic distributions at position -670, no significant difference was observed between patients and controls. At position -1377, the GG genotype and G allele was higher in the patient group than in the control group (p < 0.036). The haplotype frequencies showed a significant difference between patients and controls (p = 0.045). The association of these polymorphisms and Fas and Fas ligand serum levels and also anti-SSA/Ro and anti-SSB/La antibodies were studied in a second cohort of SLE patients. Soluble Fas and Fas ligand levels were both significantly higher in the patient group compared with controls (p = 0.001), but they showed no significant association with the studied polymorphisms. Anti-SSA/Ro and anti-SSB/La were not correlated with soluble Fas and Fas lignad levels, but patients with the -670GG genotype showed lower amounts of anti-SSB/La in their serum. In conclusion, results of this study imply that Fas promoter polymorphisms might contribute to individual susceptibility to SLE and influence the anti-SSB/La autoantibody response in patients.