Medical Parasitology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Immunology Department, Theodor Bilharz Research Institute, Cairo, Egypt.
Pathog Glob Health. 2024 Jul;118(5):429-449. doi: 10.1080/20477724.2023.2240085. Epub 2023 Jul 30.
Schistosomiasis is a neglected tropical disease. Egg-induced granuloma formation and tissue fibrosis are the main causes of the high morbidity and mortality of schistosomiasis. Mesenchymal stem cells (MSCs)-derived exosomes play an important role with a superior safety profile than MSCs in the treatment of liver fibrosis. Therefore, the aim of this study was to investigate the potential therapeutic effect of MSCs-derived exosomes on schistosomal hepatic fibrosis. Exosomes were isolated from bone marrow MSCs and characterized. A total of 85 mice were divided into four groups: group I (control group), group II (PZQ group) infected and treated with PZQ, group III (EXO group) infected and treated with MSCs-derived exosomes and group IV (PZQ+EXO group) infected and treated with both PZQ and MSCs-derived exosomes. Assessment of treatment efficacy was evaluated by histopathological and immunohistochemical examination of liver sections by proliferating cell nuclear antigen (PCNA) and nuclear factor-κB (NF-κB). The results showed significant reduction of the number and diameter of hepatic granulomas, hepatic fibrosis, upregulation of PCNA expression and reduction of NF-κB expression in EXO and PZQ+EXO groups as compared to other groups at all durations post infection. Additionally, more improvement was observed in PZQ+EXO group. In conclusion, MSCs-derived exosomes are a promising agent for the treatment of schistosomal hepatic fibrosis, and their combination with PZQ shows a synergistic action including antifibrotic and anti-inflammatory effects. However, further studies are required to establish their functional components and their mechanisms of action.
血吸虫病是一种被忽视的热带病。虫卵诱导的肉芽肿形成和组织纤维化是导致血吸虫病高发病率和高死亡率的主要原因。间充质干细胞（MSC）衍生的外泌体在治疗肝纤维化方面比 MSC 具有更好的安全性，因此在治疗肝纤维化方面具有重要作用。因此，本研究旨在探讨 MSC 衍生的外泌体治疗血吸虫性肝纤维化的潜在治疗效果。从骨髓 MSC 中分离出外泌体并进行鉴定。将 85 只小鼠分为四组：第 I 组（对照组）、第 II 组（PZQ 组）感染并接受 PZQ 治疗、第 III 组（EXO 组）感染并接受 MSC 衍生的外泌体治疗、第 IV 组（PZQ+EXO 组）感染并接受 PZQ 和 MSC 衍生的外泌体联合治疗。通过增殖细胞核抗原（PCNA）和核因子-κB（NF-κB）对肝组织切片的组织病理学和免疫组织化学检查评估治疗效果。结果显示，与其他组相比，在感染后所有时间点，EXO 和 PZQ+EXO 组肝肉芽肿的数量和直径、肝纤维化、PCNA 表达上调和 NF-κB 表达下调均显著减少。此外，PZQ+EXO 组的改善更为明显。综上所述，MSC 衍生的外泌体是治疗血吸虫性肝纤维化的一种有前途的药物，与 PZQ 联合使用具有抗纤维化和抗炎作用的协同作用。然而，需要进一步研究来确定其功能成分及其作用机制。
