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.