Abstract:
Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.
摘要:
自发性细菌性腹膜炎(SBP)是失代偿期肝硬化患者的严重并发症,通常使用广谱抗生素治疗。然而,抗生素耐药性的上升需要替代治疗策略.如最近所示,人羊膜间充质干细胞(hA-MSCs)能够,在体外,促进细菌清除并调节SBP的免疫和炎症反应。我们的结果强调了hA-MSCs中FOXO1,CXCL5,CXCL6,CCL20和MAPK13的上调以及促进细菌清除,治疗72小时后,促使免疫反应向Th17淋巴细胞表型转变。在这项研究中,我们使用体外SBP模型,并采用组学技术(下一代测序)来研究hA-MSCs修饰LPS刺激的腹水中免疫细胞间串扰的机制.我们还验证了通过qRT-PCR获得的数据,细胞荧光分析,和Luminex分析。这些发现为使用hA-MSCs预防和治疗感染性疾病的希望提供了进一步的支持。例如SBP,提供了一个可行的替代抗生素治疗。