Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Acute Lung Injury Mice

Yi Xiong,Enmei Liu,Lin Zou,Li Gao,Daiyin Tian,Rong Zhang,Yunqiu Xia,Ke Yang,Yujun Shi,Lijia Wang,Hongbing Yao,Ting Wang,Jihong Dai,Hua Zhu,Zhou Fu,Hong Jiang

doi:10.1038/srep39889

Abstract

The incidence and mortality of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still very high, but stem cells show some promise for its treatment. Here we found that intratracheal administration of human umbilical cord-mesenchymal stem cells (UC-MSCs) significantly improved survival and attenuated the lung inflammation in lipopolysaccharide (LPS)-induced ALI mice. We also used the proteins-chip and bioinformatics to analyze interactions between UC-MSCs treatment and immune-response alternations of ALI mice. Then we demonstrated that UC-MSCs could inhibit the inflammatory response of mouse macrophage in ALI mice, as well as enhance its IL-10 expression. We provide data to support the concept that the therapeutic capacity of UC-MSCs for ALI was primarily through paracrine secretion, particularly of prostaglandin-E2 (PGE2). Furthermore, we showed that UC-MSCs might secrete a panel of factors including GM-CSF, IL-6 and IL-13 to ameliorate ALI. Our study suggested that UC-MSCs could protect LPS-induced ALI model by immune regulation and paracrine factors, indicating that UC-MSCs should be a promising strategy for ALI/ARDS.

Highlights

The therapeutic effects and potential molecular mechanism of umbilical cord-mesenchymal stem cells (UC-MSCs) in an acute lung injury (ALI) model remain unclear
The results demonstrated that the total number of lung macrophages (Maker, F4/80 and CD11b) was significantly reduced in UC-MSCs-treated ALI mice, but the IL-10 positive lung macrophages (Maker, IL-10) were up-regulated (Fig. 3a,b, p < 0.05), indicating that UC-MSCs modulate the immune response of lung macrophages in ALI mice by promoting lung macrophages to secret more IL-10 to protect ALI mice
To further investigate the paracrine secretions of UC-MSCs in this mouse model of ALI, we found that a panel of the molecules secreted by the stem cells was increased significantly when cultured in bronchoalveolar lavage fluid (BALF) from ALI mouse compared with control mice (Fig. 6a)

Summary

Introduction

The therapeutic effects and potential molecular mechanism of UC-MSCs in an ALI model remain unclear. The lung injury was declined, the myeloperoxidase (MPO) activity, total protein concentration, total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) were significantly reduced, confirming that UC-MSCs attenuate the lung inflammation of LPS-induced ALI mice (Fig. 1e–h).

Results

Conclusion