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Efficacy of HGF carried by ultrasound microbubble-cationic nano-liposomes complex for treating hepatic fibrosis in a bile duct ligation rat model, and its relationship with the diffusion-weighted MRI parameters.

Abstract
Hepatic fibrosis is a major consequence of liver aggression. Finding novel ways for counteracting this damaging process, and for evaluating fibrosis with a non-invasive imaging approach, represent important therapeutic and diagnostic challenges. Hepatocyte growth factor (HGF) is an anti-fibrosis cell growth factor that induces apoptosis in activated hepatic stellate cells, reduces excessive collagen deposition, and stimulates hepatocyte regeneration. Thus, using HGF in gene therapy against liver fibrosis is an attractive approach. The aims of the present study were: (i) to explore the efficacy of treating liver fibrosis using HGF expression vector carried by a novel ultrasound microbubble delivery system; (ii) to explore the diagnostic interest of diffusion-weighted MRI (DWI-MRI) in evaluating liver fibrosis. We established a rat model of hepatic fibrosis. The rats were administered HGF linked to novel ultrasound micro-bubbles. Progression of hepatic fibrosis was evaluated by histopathology, hydroxyproline content, and DWI-MRI to determine the apparent diffusion coefficient (ADC). Our targeted gene therapy produced a significant anti-fibrosis effect, as shown by liver histology and significant reduction of hydroxyproline content. Moreover, using DWI-MRI, the b value (diffusion gradient factor) was equal to 300s/mm(2), and the ADC values significantly decreased as the severity of hepatic fibrosis increased. Using this methodology, F0-F2 could be distinguished from F3 and F4 (P<0.01). This is the first in vivo report of using an ultrasound microbubble-cationic nano-liposome complex for gene delivery. The data indicate that, this approach is efficient to counteract the fibrosis process. DWI-MRI appears a promising imaging technique for evaluating liver fibrosis.
AuthorsShou-hong Zhang, Kun-ming Wen, Wei Wu, Wen-yan Li, Jian-nong Zhao
JournalClinics and research in hepatology and gastroenterology (Clin Res Hepatol Gastroenterol) Vol. 37 Issue 6 Pg. 602-7 (Dec 2013) ISSN: 2210-741X [Electronic] France
PMID24012221 (Publication Type: Journal Article)
CopyrightCopyright © 2013. Published by Elsevier Masson SAS.
Chemical References
  • Drug Carriers
  • Liposomes
  • Phosphatidylethanolamines
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Hepatocyte Growth Factor
  • Hydroxyproline
Topics
  • Animals
  • Common Bile Duct (injuries)
  • Diffusion Magnetic Resonance Imaging
  • Disease Models, Animal
  • Drug Carriers
  • Echo-Planar Imaging
  • Gene Transfer Techniques
  • Genetic Therapy
  • Hepatocyte Growth Factor (administration & dosage, genetics)
  • Hydroxyproline (metabolism)
  • Ligation
  • Liposomes (chemistry)
  • Liver (diagnostic imaging, metabolism, pathology)
  • Liver Cirrhosis (metabolism, pathology, therapy)
  • Male
  • Microbubbles
  • Nanoparticles (chemistry)
  • Phosphatidylethanolamines
  • Polyethylene Glycols
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Sonication (methods)
  • Ultrasonography

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