Intracardiac administration for cell delivery to the kidneys and multi-modal cell tracking

Advances in Bio-Imaging (Warwick, UK) (2016) Proc Physiol Soc 36, C07

Poster Communications: Intracardiac administration for cell delivery to the kidneys and multi-modal cell tracking

L. Scarfe1,2, C. Astley2, A. Taylor1,2, P. Murray1,2, B. Wilm1,2

1. Centre for Preclinical Imaging, University of Liverpool, Liverpool, United Kingdom. 2. Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

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The most common route of cell administration in pre-clinical models is intravenous (IV)1-2. However, IV administration invariably results in cells becoming trapped in the lungs, and very few cells, if any at all, are able to escape the lungs3. We aimed to optimise an ultrasound-guided intracardiac (US-IC) method of cell administration, in order to bypass the lungs and deliver cells to the kidney. The cells were tracked using two imaging modalities, bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Female BALB/c severe combined immunodeficient (SCID) mice were administered 1 million mouse mesenchymal stem cells (mMSC) in 100µl via US-IC injection (n=4) or IV injection (n=2). mMSCs had been labelled with lentivirus-expressing luciferase for BLI, and with superparamagnetic iron oxide nanoparticles (SPIONS, ~8pg/cell) to enable MRI. Following subcutaneous injection of 150mg/kg luciferin, the mice were imaged with BLI, and subsequently with the 9.4T MR scanner (abdominal FLASH T2* scans). Mice were sacrificed immediately after imaging and organs were collected for ex vivo imaging and histology. An additional 3 mice were given US-IC injections and treated as described above, but re-imaged at 24h and 48h, and were sacrificed at 24h (n=1), or 48h (n=2). US-IC administration of mMSCs led to a whole-body distribution of bioluminescence signal, compared with IV administration, which resulted in a signal limited to the lungs. MRI scans showed a darkening of the cortex of the kidneys of mice that received a US-IC injection, indicating the presence of SPION-labelled cells in this region. In the mice that received IV administration the kidneys were comparable to baseline. To determine for how long after administration SPION-labelled cells could be detected in vivo, mice were imaged at multiple time points after US-IC cell injection. In these animals, the cortex was much lighter by 24h, and by 48h the signal was close to baseline. This change in biodistribution over time was quantified by measuring the relaxation time within the cortex, which showed a significant decrease between baseline and the day of injection (p < 0.001), and a rise in relaxation time at 24h and 48h, which was not significantly different from baseline measurements (24h, p = 0.133; 48h, p = 0.335). This was consistent with BLI data, which showed a decrease in luciferase signal over time, and histological analysis of frozen kidney sections. In conclusion, we have optimised a US-IC method of cell administration which results in successful delivery of cells to all organs of the body. With both BLI and MRI, we have successfully tracked SPION-labelled cells in the kidney, and showed that the cells were cleared from the kidney within 24h after administration.



Where applicable, experiments conform with Society ethical requirements.

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