Mesenchymal Stromal Cells for Liver Disease: A Possible Therapy for Preventing Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients withdecompensated liver cirrhosis 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. In this research project, we employed genomic and immunological analysis to investigate the mechanisms by which hA-MSCs modify the cross talk between immune cells in the ascitic fluid infected by carbapenem resistant Enterobacterales and we validated data obtained by Rats-In Vivo Experiments. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs while promoting bacterial clearance, and a shift in the immune response towards a Th17 lymphocyte phenotype after 72 hours of in vitro treatment. At the same time, the data showed a simultaneous ability of MSCs to be able to secrete cytokines necessary for the restoration of normal physiological conditions, after theresolution of the infection. This data suggests an importance in the application of this possible therapeutic strategy as the ability of hA-MSCs to exercise both functions, anti-bacterial capacity and anti-inflammatory activity following resolution of the infection, allows to create a correct physiological balance and avoid a possible development of autoimmune diseases.The results were validated by In-vivo data performed on immunocompetent rats in which blood and biochemical parameters showed a benefit of treatment with a single infusion of MSCs 1 week after treatment. MRI image acquisition supported the results by highlighting a principle of tissue damage at the abdominal level in rats not subjected to therapeutic treatment with hA-MSC. In conclusion, these findings provide further support to use hA-MSCs for the prevention and treatment of SBP, offering a viable alternative to antibiotic therapy.