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Lung

, Volume 193, Issue 1, pp 85–95 | Cite as

Infusion of Mesenchymal Stem Cells Protects Lung Transplants from Cold Ischemia-Reperfusion Injury in Mice

  • Weijun Tian
  • Yi Liu
  • Bai Zhang
  • Xiangchen Dai
  • Guang Li
  • Xiaochun Li
  • Zhixiang Zhang
  • Caigan DuEmail author
  • Hao WangEmail author
Article

Abstract

Background

Cold ischemia-reperfusion injury (IRI) is a major cause of graft failure in lung transplantation. Despite therapeutic benefits of mesenchymal stem cells (MSCs) in attenuating acute lung injury, their protection of lung transplants from cold IRI remains elusive. The present study was to test the efficacy of MSCs in the prevention of cold IRI using a novel murine model of orthotopic lung transplantation.

Methods

Donor lungs from C57BL/6 mice were exposed to 6 h of cold ischemia before transplanted to syngeneic recipients. MSCs were isolated from the bone marrows of C57BL/6 mice for recipient treatment. Gas exchange was determined by the measurement of blood oxygenation, and lung injury and inflammation were assessed by histological analyses.

Results

Intravenously delivered MSC migration/trafficking to the lung grafts occurred within 4-hours post-transplantation. As compared to untreated controls, the graft arterial blood oxygenation (PaO2/FiO2) capacity was significantly improved in MSC-treated recipients as early as 4 h post-reperfusion and such improvement continued over time. By 72 h, oxygenation reached normal level that was not seen in controls. MSCs treatment conferred significant protection of the grafts from cold IRI and cell apoptosis, which is correlated with less cellular infiltration, a decrease in proinflammatory cytokines (TNF-α, IL-6) and toll-like receptor 4, and an increase in anti-inflammatory TSG-6 generation.

Conclusions

MSCs provide significant protection against cold IRI in lung transplants, and thus may be a promising strategy to improve outcomes after lung transplantation.

Keywords

Mesenchymal stem cells Orthotopic lung transplantation Cold ischemia-reperfusion injury Mice 

Abbreviations

ANOVA

Analysis of variance

eGFF

Enhanced green fluorescence protein

H&E

Hematoxylin & eosin

MSCs

Mesenchymal stem cells

IL

Interleukin

IRI

Ischemia-reperfusion injury

ROS

Reactive oxygen species

SEM

Standard error of mean

TNF

Tumor necrosis factor

TLR

Toll-like receptor

TSG

Tumor necrosis factor-α stimulated gene/protein

TUNEL

Terminal deoxynucleotyl transferase dUTP nick end labeling

Notes

Acknowledgments

We are grateful to Dr. Bertha Garcia at Western University, London, Canada for her critical review of the histological slides, and to Drs. Shuhua Luo and Weihua Liu for their technical assistance. This work was supported by Grant to H.W. from National Natural Science Foundation of China (No. 81273257), and National High Technology Research and Development Program 863 (2012AA021003). C.D. was supported by grants from the Kidney Foundation of Canada and the Canadian Institutes of Health Research.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Weijun Tian
    • 1
  • Yi Liu
    • 2
  • Bai Zhang
    • 1
  • Xiangchen Dai
    • 1
  • Guang Li
    • 2
  • Xiaochun Li
    • 3
  • Zhixiang Zhang
    • 1
    • 4
  • Caigan Du
    • 5
    • 6
    Email author
  • Hao Wang
    • 1
    • 4
    Email author
  1. 1.Department of General SurgeryTianjin Medical University General HospitalTianjinChina
  2. 2.Department of BiologyTianjin Medical UniversityTianjinChina
  3. 3.Department of CardiologyTianjin Medical University General HospitalTianjinChina
  4. 4.Tianjin General Surgery InstituteTianjinChina
  5. 5.Immunity and Infection Research CentreVancouver Coastal Health Research InstituteVancouverCanada
  6. 6.Department of Urologic SciencesThe University of British Columbia, VGH-Jack Bell Research CentreVancouverCanada

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