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Hepatocyte growth factor-modified mesenchymal stem cells improve ischemia/reperfusion-induced acute lung injury in rats

Gene Therapy volume 24, pages 3–11 (2017)Cite this article

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Abstract

Accumulative evidence demonstrated that mesenchymal stem cell (MSC) engraftment could protect tissue injury from ischemia/reperfusion (I/R). Hepatocyte growth factor (HGF) has important roles in the cell and tissue repairment and regeneration. Here we investigated the enhanced effects of HGF-modified MSCs on I/R-induced acute lung injury. Rat bone marrow-derived MSCs were successfully transfected to express HGF. HGF modification did not affect the characteristics of MSCs, and increased MSC viability, and inhibit the proinflammatory phenotype of MSCs in the inflammatory condition. In the rat model of I/R-induced lung injury, MSC-HGF engraftment attenuated lung wet-to-dry weight ratio, enhanced PaO2 level and improved lung pathological injury, compared with MSC treatment. Moreover, the decreased acitivity of malondialdehyde, myeloperoxidase and tumor necrosis factor-α and increased superoxide dismutase content and interleukin-10 level were also observed in the MSC-HGF treatment, compared with the MSC group. Importantly, we found that HGF contributed to the survival of engrafted MSCs in the lung tissue through upregulation of Bcl-2 level and reduction of Caspase 3 activation. Thus our data show for the first time a clear beneficial effect of HGF gene modification on the survival of MSCs and enhanced improvement for I/R-induced lung injury.

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Abbreviations

MSC:

mesenchymal stem cell

HGF:

hepatocyte growth factor

I/R:

ischemia/reperfusion

rAV:

recombinant adenoviral vector

GFP:

green fluorescent protein

PBS:

phosphate-buffered saline

PAEC:

pulmonary alveolar epithelial cell

TUNEL:

terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end

MPO:

myeloperoxidase

MAL:

malondialdehyde

SOD:

superoxide dismutase.

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Acknowledgements

This study was supported by a grant from Natural Science Foundation of China (grant NSFC 81341006) and the Natural Science Foundation of Fujian province (grant 2013J05116).

Author contributions

Shuchen Chen and Xiangqi Chen participated in research design, performance of research and writing of the article. Xiaonan Wu participated in the performance of the research. Shijin Wei participated in research design. Wu Han participated in research design and evaluation of the research. Jihong Lin participated in analyzing and interpreting the data. Mingqiang Kang and Liangwan Chen participated in financial support, research design and writing of the article.

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Author notes

  1. S Chen and X Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China

    S Chen, W Han, J Lin & M Kang

  2. Fujian Institute of Cardio-Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China

    S Chen, W Han, J Lin, M Kang & L Chen

  3. Department of Respiratory Diseases, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China

    X Chen

  4. School of Public Health, Fujian Medical University, Fuzhou, People’s Republic of China

    X Wu

  5. Blood Bank, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China

    S Wei

  6. Department of Cardiac Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China

    L Chen

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Correspondence to M Kang or L Chen.

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Chen, S., Chen, X., Wu, X. et al. Hepatocyte growth factor-modified mesenchymal stem cells improve ischemia/reperfusion-induced acute lung injury in rats. Gene Ther 24, 3–11 (2017). https://doi.org/10.1038/gt.2016.64

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