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Structural impact of hydrodynamic injection on mouse liver

Gene Therapy volume 14, pages 129–137 (2007)Cite this article

Abstract

The impact of hydrodynamic injection on liver structure was evaluated in mice using various microscopic techniques. Upon hydrodynamic injection of approximately 9% of body weight by volume, the liver rapidly expanded, reaching maximal size at the end of the injection and returned to its original size in 30 min. Histological analysis revealed a swollen appearance in the peri-central region of the liver where delivery of genes and fluorescence-labeled markers was observed. Scanning and transmission electron microscopy showed enlargement and rupture of endothelium that in about 24–48 h regains its morphology and normal function as a barrier against infection by adenovirus viral particles. At the cellular level in hydrodynamically treated animals, four types of hepatocytes were seen: cells with normal appearance; cells with enriched vesicles in the cytoplasm; cells with lightly stained cytosol; and cells with significant dilution of the cytoplasm. In addition, red blood cells and platelets were observed in the space of Disse and even inside hepatocytes. Vesicle formation is triggered by hydrodynamic injection and resembles the process of macropinocytosis. These results, whereas confirming the physical nature of hydrodynamic delivery, are important for a better understanding of this efficient method for intrahepatic gene and small interfering RNA delivery.

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Acknowledgements

We thank Dr Song Li for providing us with adenoviral vectors. We thank Dr Joseph E Knapp for critical review of the paper. This work was supported in part by NIH Grants EB2002946 and HL075542.

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Author notes

  1. X Gao

    Present address: PGR-Solutions Inc., Bridgeville, PA, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    T Suda, X Gao & D Liu

  2. Department of Cell Biology and Physiology, Center for Biologic Imaging, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    D B Stolz

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  1. T Suda
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  2. X Gao
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  3. D B Stolz
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  4. D Liu
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Correspondence to D Liu.

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Suda, T., Gao, X., Stolz, D. et al. Structural impact of hydrodynamic injection on mouse liver. Gene Ther 14, 129–137 (2007). https://doi.org/10.1038/sj.gt.3302865

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