Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography

Transplantation of primary human hepatocytes is a promising approach in certain liver diseases. For the visualization of the hepatocytes during and following cell application and the ability of a timely response to potential complications, a non-invasive modality for imaging the transplanted cells has to be established. The aim of this study was to label primary human hepatocytes with micron-sized iron oxide particles (MPIOs), enabling the detection of cells by clinical magnetic resonance imaging (MRI). Primary human hepatocytes isolated from 13 different donors were used for the labelling experiments. Following the dose-finding studies, hepatocytes were incubated with 30 particles/cell for 4 hrs in an adhesion culture. Particle incorporation was investigated via light, fluorescence and electron microscopy, and labelled cells were fixed and analysed in an agarose suspension by a 3.0 Tesla MR scanner. The hepatocytes were enzymatically resuspended and analysed during a 5-day reculture period for viability, total protein, enzyme leakage (aspartate aminotransferase [AST], lactate dehydrogenase [LDH]) and metabolic activity (urea, albumin). A mean uptake of 18 particles/cell could be observed, and the primary human hepatocytes were clearly detectable by MR instrumentation. The particle load was not affected by resuspension and showed no alternations during the culture period. Compared to control groups, labelling and resuspension had no adverse effects on the viability, enzyme leakage and metabolic activity of the human hepatocytes. The feasibility of preparing MPIO-labelled primary human hepatocytes detectable by clinical MR equipment was shown in vitro. MPIO-labelled cells could serve for basic research and quality control in the clinical setting of human hepatocyte transplantation

Spearman correlation coefficients of selected fasting serum NEFA species with parameters of body composition.

<p>All nonesterified fatty acid (NEFA) species with a Spearman correlation coefficient ρ≥0.3 with any of the listed parameters of body composition are shown in the table. The post-GDM and the control group were combined for this analysis. n = 106 for BMI, WC and percent body fat measured by BIA. n = 62 for the MRI substudy.</p><p>*Correlation is significant with p<0.05.</p><p>**Correlation is significant with p<0.01.</p><p>***Correlation is significant with p<0.001.</p><p>Spearman correlation coefficients of selected fasting serum NEFA species with parameters of body composition.</p

Clinical and biochemical characteristics of the study cohort.

<p>The values are represented as the medians with interquartile ranges. If not stated otherwise n = 62 for the cases and n = 49 for the controls.</p><p>^*Chi-Square test.</p><p>^#(n = cases/controls).</p><p>^aabdominal.</p><p>^bAdipocyte-IR Index = fasting total NEFA_LC-MS/MS (μM) * fasting insulin (μU/ml).</p><p>Clinical and biochemical characteristics of the study cohort.</p

Plasma concentrations of selected biomarkers.

<p>The values are represented as the medians with interquartile ranges.</p><p>Plasma concentrations of selected biomarkers.</p