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

Int J Mol Sci. 2022 Jan 13;23(2):857. 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.

Keywords: ascitic fluid; carbapenem-resistant Enterobacterales; cirrhosis; complement; ficolins; human amnion-derived mesenchymal stromal cells; pattern recognition molecules; placenta; spontaneous bacterial peritonitis.

MeSH terms

  • Amnion / cytology*
  • Bacterial Load
  • Biomarkers
  • Carbapenems / pharmacology
  • Complement Activation / immunology
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Disease Susceptibility
  • Enterobacter / drug effects
  • Enterobacter / genetics
  • Enterobacteriaceae Infections / complications
  • Enterobacteriaceae Infections / microbiology
  • Humans
  • Immunomodulation
  • Inflammation Mediators
  • Macrophages
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Peritoneal Fibrosis / etiology*
  • Peritoneal Fibrosis / metabolism
  • Peritoneal Fibrosis / therapy*
  • Peritonitis / complications
  • Peritonitis / microbiology
  • Phagocytosis
  • Receptors, Pattern Recognition / metabolism
  • Treatment Outcome
  • beta-Lactam Resistance

Substances

  • Biomarkers
  • Carbapenems
  • Inflammation Mediators
  • Receptors, Pattern Recognition
  • Complement System Proteins