الفهرس | Only 14 pages are availabe for public view |
Abstract Praziquantel (PZQ) is the current drug of choice recommended for the treatment of schistosomiasis, however the potential of drug resistance remains a major concern. Mesenchymal stem cells (MSCs)-derived exosomes play an important role in the therapeutic effect of MSCs. MSCs-derived exosomes exhibit a superior safety profile as their use rather than cells avoids the risks of MSCs. This study aimed to investigate the potential therapeutic effect of MSCs-derived exosomes on hepatic fibrosis in Schistosoma mansoni-infected mice. For this aim, exosomes were isolated from bone marrow MSCs and characterized. A total of 250 male Swiss albino mice were divided into four groups including group I (control group), group II (PZQ group) infected and treated with PZQ at 6 weeks post infection (P.I.), group III (EXO group) was subdivided into two subgroups (IIIa: infected and treated with MSCs-derived exosomes at 6 weeks P.I. and IIIb: received MSCs-derived exosomes at 10 weeks P.I.) and group IV (PZQ+EXO group) was subdivided into two subgroups (IVa: infected and treated with both PZQ and MSCs-derived exosomes 6 weeks P.I. and IVb: received PZQ at 6 weeks P.I. and MSCs-derived exosomes at 10 weeks P.I.). Infected mice that were treated with exosomes were sacrificed 2 and 4 weeks post treatment. Control infected and PZQ-treated groups were sacrificed at the corresponding time periods. Assessment of treatment efficacy was evaluated by: histopathological and immunohistochemical examination for liver sections by proliferating cell nuclear antigen (PCNA) and nuclear factor-kappa B (NF-κB) and measurement of liver enzymes. The results showed significant reduction in the number and diameter of hepatic granulomas and in hepatic fibrosis, upregulation of PCNA expression, reduction of NF-κB expression and decrease in the serum levels of alanine transaminase and aspartate transaminase in EXO and PZQ+EXO groups as compared to other groups at all durations P.I. Additionally, more improvement was observed in PZQ+EXO group. In conclusion, combination of MSCs-derived exosomes with PZQ shows a synergistic action in the treatment of S. mansoni-infected mice including anti-fibrotic and anti-inflammatory effects. Therefore, MSCs-derived exosomes are a promising agent for the treatment of schistosomal hepatic fibrosis. Further studies are required to establish their functional components and their mechanisms of action. |