Int J Med Sci 2019; 16(9):1238-1244. doi:10.7150/ijms.35369

Research Paper

Exosomes Released by Bone Marrow Mesenchymal Stem Cells Attenuate Lung Injury Induced by Intestinal Ischemia Reperfusion via the TLR4/NF-κB Pathway

Janpei Liu1*, Tufeng Chen1*, Purun Lei1, Xiao Tang1, Pinjie Huang2✉

1. Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 510630.
2. Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 510630.
* contributed equally to this work.

Abstract

Purpose: Acute lung injury (ALI) is a primary component of multiple organ dysfunction syndromes triggered by intestinal ischemia-reperfusion (IIR) which results in high mortality. Existing treatment options remain unsatisfactory. Mesenchymal stem cells (MSCs) have shown considerable promise as a biological therapy for ALI in preclinical studies. However, there are many limitations to stem cell treatment. This study aimed to investigate whether MSC-derived exosomes, a non-cellular alternative, are able to act in a protective capacity similar to that of MSCs for ALI triggered by IIR in a rat model and to explore the underlying mechanisms.

Methods: The IIR model involved occlusion of the superior mesenteric artery of a rat for 75 min then reperfusion for 20 h. Rats then received an intravenous injection of either bone marrow-derived MSCs or MSC-derived exosomes. Pathologic alteration of lung tissue, levels of pro-inflammatory cytokines, apoptotic proteins and TLR4/NF-κB signaling were measured to evaluate the therapeutic effect of treatment with either MSCs or exosomes.

Results: Manifestations of acute lung injury after IIR were observed as edema and hemorrhage of alveoli and mesenchyme, and inflammatory cell infiltration. MSCs and MSC-derived exosomes both attenuated IIR-induced lung damage by decreased apoptosis and inflammation accompanied by down-regulation of TLR4 and NF-κB expression.

Conclusions: MSC-derived exosomes provide protection similar to that of MSCs against IIR-induced ALI via inhibition of TLR4/NF-κB signaling, suggesting that a potential strategy against IIR-mediated acute lung injury could be therapy with exosomes as a non-cellular alternative to MSC transplantation.

Keywords: Mesenchymal stem cell, exosome, ischemia reperfusion, intestine, lung injury, Toll-like receptor 4.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Liu J, Chen T, Lei P, Tang X, Huang P. Exosomes Released by Bone Marrow Mesenchymal Stem Cells Attenuate Lung Injury Induced by Intestinal Ischemia Reperfusion via the TLR4/NF-κB Pathway. Int J Med Sci 2019; 16(9):1238-1244. doi:10.7150/ijms.35369. Available from http://www.medsci.org/v16p1238.htm