Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation

Int J Mol Sci. 2024 Feb 28;25(5):2801. doi: 10.3390/ijms25052801.

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.

Keywords: ascitic fluid; cirrhosis; human amnion-derived mesenchymal stromal cells; lipopolysaccharide; placenta; spontaneous bacterial peritonitis.

MeSH terms

  • Amnion
  • Anti-Bacterial Agents / therapeutic use
  • Ascites
  • Ascitic Fluid / microbiology
  • Bacterial Infections* / microbiology
  • Forkhead Box Protein O1
  • Humans
  • Lipopolysaccharides
  • Liver Cirrhosis / complications
  • Peritonitis* / drug therapy

Substances

  • Lipopolysaccharides
  • Anti-Bacterial Agents
  • FOXO1 protein, human
  • Forkhead Box Protein O1

Grants and funding

This study was supported by Ri.MED Foundation funds and the Italian Ministry of Health through Ricerca Corrente funds.