Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen

Ya Lin Huang, Cristian De Gregorio, Verónica Silva, Álvaro A. Elorza, Patricio Léniz, Víctor Aliaga-Tobar, Vinicius Maracaja-Coutinho, Mauricio Budini, Fernando Ezquer, Marcelo Ezquer

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.

Original languageEnglish
Article number636
JournalCells
Volume12
Issue number4
DOIs
Publication statusPublished - Feb 2023

Keywords

  • amiodarone
  • cell free therapy
  • drug-induced liver injury
  • hepatic regeneration
  • tamoxifen

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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