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

Salvatore Gruttadauria,Alessandra Mularoni,Pier Giulio Conaldi,Mariangela Pampalone,Giada Pietrosi,Giampiero Vitale,Gioacchin Iannolo,Giandomenico Amico,Bruno Douradinha

doi:10.3390/ijms23020857

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.

Highlights

Spontaneous bacterial peritonitis (SBP) is the most relevant infectious complication, developing in 10–25% of patients with decompensated cirrhosis with ascites [1,2], causing about 5–25% mortality in cirrhotic patients awaiting liver transplantation [3]
To determine the ability of Human amniotic mesenchymal stromal cells (hA-mesenchymal stem cells (MSC)) to impair Enterobacterales growth levels, ascitic fluid (AF) collected from cirrhotic patients was infected with the aforementioned microorganisms, and the bacterial loads were quantified at different time points
We used hA-MSC grown in Roswell Park Memorial Institute (RPMI) without antibiotics (Control 1) and white blood cell AF (WBCsAF) without hA-MSCs (Control 2); the latter was to evaluate how the presence of white blood cells (WBCs) in AF may affect its capability to inhibit bacterial growth

Summary

Introduction

Spontaneous bacterial peritonitis (SBP) is the most relevant infectious complication, developing in 10–25% of patients with decompensated cirrhosis with ascites [1,2], causing about 5–25% mortality in cirrhotic patients awaiting liver transplantation [3]. Regardless of the mechanism through which bacteria reach the ascitic fluid (AF), the probability of developing an infection is inversely proportional to the bactericidal capacity of the ascites themselves, through the activation of humoral bactericidal mechanisms, mainly the complement system [6]. This system includes three activation pathways; the classical pathway, the lectin pathway, and the alternative pathway [7]. We have previously shown that human amnion-derived mesenchymal cells (hA-MSCs) are able to increase anti-inflammatory cytokines and induce an M2-biased polarization in AF macrophages. 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

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Conclusion