Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis

Abstract

Background: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. Methods: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenem-resistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macrophage phenotypic expression. Results: hA-MSCs added to AF significantly reduce the proliferation of both bacterial strains at 24 h and diversely affect M1 and M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection, in a bacterial strain-dependent fashion. Conclusion: This study shows the potential usefulness of hA-MSC in treating ascites infected with carbapenem-resistant bacteria and lays the foundation to further investigate antibacterial and anti-inflammatory roles of hA-MSC in in vivo models.

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

“…Alternative immune therapies that can decrease bacterial proliferation are under evaluation [ 35 , 36 , 50 , 51 ]. Regenerative medicine holds potential for addressing this issue by modulating the expression of specific immunological targets, which can reduce bacterial load and restore homeostasis.…”

“…Our group has recently shown, in vitro, that by co-culturing hA-MSCs with infected ascites obtained from patients with cirrhosis with refractory ascites, these stem cells exhibit antibacterial properties, modulate inflammatory cytokine pathways [ 32 , 33 , 34 ], stimulate the production of anti-inflammatory cytokines, and mediate a balanced immune response toward a resolution of the infection [ 35 ]. hA-MSCs have been found to promote anti-inflammatory M2 macrophage polarization without affecting the phagocytosis activity of macrophages and NK cells, reduce C3a complement protein and Ficolin-3 concentrations during the course of infection, and significantly decrease the proliferation of common carbapenem-resistant Enterobacterales strains responsible for SBP, including E. coli and Klebsiella pneumonia [ 36 ].…”

“…Therefore, hA-MSC-based cell therapy represents a promising avenue for the prevention and treatment of SBP, offering a viable alternative to antibiotic therapy [ 36 ].…”

Spontaneous Bacterial Peritonitis in Decompensated Liver Cirrhosis—A Literature Review

“…One potential approach is human amniotic mesenchymal stromal cell (hA-MSC) treatment. One in vitro study found hA-MSCs added to ascites fluid could significantly reduce the proliferation of both bacterial strains at 24 h as well as affect M1/M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection in a strain-dependent manner [101]. Validation of an in vivo model is warranted for future hA-MSC application in treating ascites infected with carbapenemresistant bacteria [101].…”