Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p.

Abstract:

BACKGROUND:Using a toxin-induced nonhuman primate model of acute liver failure (ALF), we previously reported that peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) strongly suppresses the activation of circulating monocytes and interleukin-6 (IL-6) production, thereby disrupting the development of a cytokine storm and improving the prognosis of monkeys. MSCs are considered to play a therapeutic role under different stresses by adaptively producing specific factors, prompting us to investigate the factors that hUC-MSCs produce in response to high serum levels of IL-6, which plays a critical role in initiating and accelerating ALF. METHODS:We stimulated hUC-MSCs with IL-6, and the hUC-MSC-derived exosomes were deeply sequenced. The miRNAs in the exosomes that have potential to suppress IL-6-associated signaling pathway were screened, and the role of one of the most possible miRNAs was tested in the mouse model of inflammatory liver injury. RESULT:We determined that miR-455-3p, which is secreted through exosomes and potentially targets PI3K signaling, was highly produced by hUC-MSCs with IL-6 stimulation. The miR-455-3p-enriched exosomes could inhibit the activation and cytokine production of macrophages challenged with lipopolysaccharide (LPS) both in vivo and in vitro. In a chemical liver injury mouse model, enforced expression of miR-455-3p could attenuate macrophage infiltration and local liver damage and reduce the serum levels of inflammatory factors, thereby improving liver histology and systemic disorder. CONCLUSIONS:miR-455-3p-enriched exosomes derived from hUC-MSCs are a promising therapy for acute inflammatory liver injury.

journal_name

Stem Cell Res Ther

authors

Shao M,Xu Q,Wu Z,Chen Y,Shu Y,Cao X,Chen M,Zhang B,Zhou Y,Yao R,Shi Y,Bu H

doi

10.1186/s13287-020-1550-0

subject

Has Abstract

pub_date

2020-01-23 00:00:00

pages

37

issue

1

issn

1757-6512

pii

10.1186/s13287-020-1550-0

journal_volume

11

pub_type

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