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Kelsey Paige Kubelick, Eric Snider, Andrei Karpiouk, C Ross Ethier, Stanislav Emelianov; Nanoparticle-augmented ultrasound and photoacoustic imaging to track stem cells in the anterior eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6132.
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© ARVO (1962-2015); The Authors (2016-present)
Novel glaucoma treatments seek to deliver stem cells to regenerate the trabecular meshwork (TM) and thus reduce IOP. Histology is the gold standard for monitoring stem cell localization, but destructive sample preparation limits its use. To expedite development and clinical translation, longitudinal stem cell tracking in vivo is desirable. Thus, we are developing an ultrasound and photoacoustic (US/PA) imaging platform for tracking mesenchymal stem cells (MSCs) in the anterior eye.
After analysis of the PA properties of anterior segment tissues in blue and brown porcine eyes, human MSCs were tagged with one of two custom-made optical absorbers: gold nanospheres (AuNSs) or Prussian blue nanocubes (PBNCs). MSCs were tagged by incubation with particles in vitro and then collected and washed to remove excess particles. Tagged MSCs were injected (250 µL at 1,000-4,000 cells/µL) into porcine anterior segments in culture and perfused with media at a physiological flow rate of 2.5 µL/min to circulate tagged MSCs in the anterior chamber. US/PA datasets were acquired for up to 5 hours post-injection using the Vevo 2100 (20 MHz ultrasound transducer) and LAZR (680-970 nm wavelength range). Eye globes were dissected for histology and further spectroscopic PA imaging to verify results.
Ultrasound imaging visualized anatomical landmarks (gray scale), and melanin-rich tissues produced strong signals with single-wavelength PA imaging (red scale) (Fig 1A). An increase in PA signal upon injection of AuNS-MSCs was observed (Fig 1B). The imaging platform was further developed to include 3D US/PA imaging (Fig 1C). Multi-wavelength PA imaging and spectroscopic analysis distinguished AuNS-MSCs and melanin at 5 hours post-injection (Fig 1D). To improve delivery efficiency, we used photomagnetic PBNC-MSCs; as proof-of-concept, a disc magnet pulled PBNC-MSCs to the cornea and held the cells in place for 24 hours (Fig 1E).
Our US/PA imaging platform has the ability to monitor stem cell location in the anterior eye, specifically facilitating real-time image-guided delivery with potential for longitudinal monitoring in vivo. Current efforts focus on magnetic guidance to the TM to improve delivery efficiency (Fig 1F).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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