Ultrasound‐guided hepatic portal vein injection is not a reproducible technique for delivery of cell therapies to the liver in mice

Aims: Our aim was to determine if ultrasound-guided HPV injection in mice
would provide reproducible and reliable results, as is currently obtained via open
laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans.
Methods: Fluorescent-polymer microparticles (20μm) were injected (27Gneedle) into the HPV via open laparotomy (n=4) or under ultrasound-guidance
(n=4) using an MX550D-transducer with a Vevo3100-scanner (FUJIFILM
VisualSonics, Inc.). Mice were culled 24-h post injection; organs were frozen, step sectioned (10μm-slices) and 10 sections/mouse (50μm-spacing) were quantified
for microparticles in the liver and other organs by fluorescent microscopy.
Results: Murine HPV injection, via open laparotomy-route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasoundguided injection resulted in reduced microparticle delivery (p<0.0001) and
microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median (interquartile
range) 4.15 (0.00–4.15) versus 0.00 (0.00–0.00) particle-count mm−2, respectively.
Conclusions: Ultrasound-guided injection results in microparticle clustering in
the liver, with an overall reduction in microparticle number when compared to
open laparotomy HPV injection, and high variability in microparticle-counts detected between mice. Ultrasound-guided injection is not currently a technique
that can replace open laparotomy HPV of islet transplantation in mice.