Research Papers:
Combination therapy of human umbilical cord mesenchymal stem cells and FTY720 attenuates acute lung injury induced by lipopolysaccharide in a murine model
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Abstract
Zili Zhang1,2,4,*, Wenfei Li3,*, Zhizhi Heng1, Jing Zheng1, Puyuan Li1, Xin Yuan1, Wenkai Niu1, Changqing Bai1 and Huiying Liu1
1Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA, Beijing 100071, China
2Anhui Medical University, Hefei 230032, China
3School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, China
4Beijing Geriatric Hospital, Beijing 100095, China
*These authors have contributed equally to this work
Correspondence to:
Changqing Bai, email: [email protected]
Huiying Liu, email: [email protected]
Keywords: acute lung injury, lipopolysaccharide, hUC-MSCs, FTY720, Sphingosine-1-phosphate
Received: June 01, 2017 Accepted: July 26, 2017 Published: August 24, 2017
ABSTRACT
ALI/ARDS remain the main reason of morbidity and mortality in the critically ill. Studies have indicated that human umbilical cord mesenchymal stem cells (hUC-MSCs) can be useful in the treatment of ALI/ARDS. Sphingosine-1-phosphate (S1P) and its analog FTY720 significantly reduce lipopolysaccharide (LPS)-induced lung edema and inflammatory lung injury. This study aimed to assess the therapeutic effects of hUC-MSCs combined with FTY720 in an LPS-induced murine model of ALI. Eight-week-old female C57BL/6 mice were divided into a normal control group, an LPS group, an hUC-MSC group, an FTY720 group, and an hUC-MSCs+FTY720 group randomly. At 24 hours post injury, mice were administrated hUC-MSCs via the tail vein and/or intraperitoneally injected with FTY720. We assessed histopathology and histologic scores, lung wet/dry weight ratio, micro-CT scans, and total protein in the bronchoalveolar lavage fluid (BALF), as well as cytokines in the BALF at 48 h post injury. All treatment groups showed higher survival rates and attenuated lung injuries. The hUC-MSCs+FTY720 group yielded better results than hUC-MSCs or FTY720 alone. While the underlying mechanism requires further study, we anticipate that combination therapy of hUC-MSCs and FTY720 could be an effective strategy for ALI.
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