A Augello

A Jain

A Krasnodembskaya

A Uccelli

AC Bulua

C Cai

CC Santos dos

CS Deutschman

E Xiao

G Fang

G Ren

GM Fimia

GM Spaggiari

II Siempos

K Balmanno

K Blanc Le

K Degenhardt

K Németh

L Bai

L Dejager

L Yu

MB Azad

MC Tal

ME Bernardo

MJ Morgan

N Kusadasi

N Mizushima

N Totsuka

NG Singer

P Wild

PT Brinkkoetter

R Scherz-Shouval

S Aggarwal

S Dang

SR Hall

TP Rygiel

Y Liu

Y Shi

Abstract
                Background
                Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified.
              
                Methods
                We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs.
              
                Results
                Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway.
              
                Conclusions
                Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.
              </jats:sec

Shipeng Dang

Zhi-ming Yu

Chang-ying Zhang

Jie Zheng

Ku-lin Li

Ying Wu

Ling-ling Qian

Zhen-yu Yang

Xiao-rong Li

Yanyun Zhang

Ru-xing Wang

Crossref

Stem Cell Research & Therapy

Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment

https://stemcellres.biomedcentral.com/track/pdf/10.1186/s13287-015-0245-4?site=stemcellres.biomedcentral.com

Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment

Abstract

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