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

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.

Cite this document

Huang, Y.-L., De Gregorio, C., Silva, V., Elorza, Á. A., Léniz, P., Aliaga-Tobar, V., Maracaja-Coutinho, V., Budini, M., Ezquer, F., & Ezquer, M. (2023). 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. Cells, 12(4), 636. https://doi.org/10.3390/cells12040636

Project(s)

Investigating the role of skin microbiome, host immunity and infection in epidermolysis bullosa wound healing

The therapeutic potential of three-dimensional multipotent mesenchymal stromal cell spheroids for the treatment of Acute on Chronic Liver Failure: the shield that could protect against the inflammatory storm

Subjects

amiodarone

;

cell free therapy

;

drug-induced liver injury

;

hepatic regeneration

;

tamoxifen

;

amiodarone

;

animals

;

chemical and drug induced liver injury

;

fatty liver

;

humans

;

immunologic factors

;

mesenchymal stem cells

;

mice

;

mice, inbred c57bl

;

secretome

;

tamoxifen

;

alanine aminotransferase

;

alpha smooth muscle actin

;

amiodarone

;

aspartate aminotransferase

;

caspase 3

;

caspase 7

;

cd3 antigen

;

cholesterol 7alpha monooxygenase

;

cytochrome c

;

cytochrome p450 1a1

;

cytochrome p450 1a2

;

cytochrome p450 2b6

;

cytochrome p450 2c19

;

cytochrome p450 2c9

;

cytochrome p450 2d6

;

cytochrome p450 2e1

;

cytochrome p450 3a4

;

dichlorodihydrofluorescein diacetate

;

dimethyl sulfoxide

;

gentamicin

;

glyceraldehyde 3 phosphate dehydrogenase

;

hydrogen peroxide

;

inducible nitric oxide synthase

;

interleukin 6

;

ki 67 antigen

;

lactate dehydrogenase

;

nuclear protein

;

reactive oxygen metabolite

;

ribosomal protein l13a

;

succinate dehydrogenase

;

tamoxifen

;

tumor necrosis factor

;

unclassified drug

;

amiodarone

;

immunologic factor

;

tamoxifen

;

animal experiment

;

animal model

;

animal tissue

;

apoptosis

;

article

;

autofluorescence

;

cell free system

;

cell infiltration

;

cell proliferation

;

cell stimulation

;

cell viability

;

confocal microscopy

;

controlled study

;

drug cytotoxicity

;

drug-induced liver injury

;

fatty liver

;

fetal bovine serum

;

fibrogenesis

;

fluorescence microscopy

;

gene expression

;

hep-g2 cell line

;

heparg cell line

;

histogram

;

human

;

human cell

;

human tissue

;

idiosyncratic drug reaction

;

immunofluorescence

;

immunohistochemistry

;

immunoreactivity

;

in vitro study

;

in vivo study

;

liver histology

;

liver protection

;

liver regeneration

;

male

;

mesenchymal stem cell

;

mouse

;

mtt assay

;

nonhuman

;

obesity

;

proteomics

;

real time reverse transcription polymerase chain reaction

;

rna isolation

;

secretome

;

tunel assay

;

animal

;

c57bl mouse

;

fatty liver

;

metabolism

;

toxic hepatitis