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Constitutive and Inducible Systems for Genetic In Vivo Modification of Mouse Hepatocytes Using Hydrodynamic Tail Vein Injection
Published on: February 2, 2018
Structural impact of hydrodynamic injection on mouse liver
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Gene Therapy
|September 22, 2006
Summary
Hydrodynamic injection causes rapid liver expansion and endothelial cell changes in mice. This method efficiently delivers genes and RNA, with hepatocytes showing varied responses and cellular changes.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Biology
Background:
- Hydrodynamic injection is an efficient method for in vivo gene and small interfering RNA delivery to the liver.
- Understanding the cellular and structural impact of this technique is crucial for optimizing its application.
Purpose of the Study:
- To investigate the effects of hydrodynamic injection on mouse liver structure and cellular morphology.
- To elucidate the dynamic changes in liver endothelium and hepatocytes following hydrodynamic delivery.
Main Methods:
- Mice underwent hydrodynamic injection (approx. 9% body weight).
- Microscopic techniques including histology, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were employed.
- Analysis focused on liver structure, endothelial integrity, and hepatocyte morphology.
Main Results:
- The liver rapidly expanded and then returned to normal size within 30 minutes post-injection.
- Histology showed peri-central swelling, while SEM/TEM revealed endothelial cell enlargement and rupture, with recovery in 24-48 hours.
- Hepatocytes exhibited diverse changes, including vesicle enrichment and cytoplasmic dilution; red blood cells and platelets were found in the space of Disse and within hepatocytes.
Conclusions:
- Hydrodynamic injection induces significant, transient physical changes in liver structure and endothelium.
- Hepatocyte responses include vesicle formation resembling macropinocytosis.
- These findings enhance the understanding of hydrodynamic delivery's efficiency and safety for intrahepatic gene and RNA therapeutics.
