Imaging Stem Cell Delivery Near the Bed: Are We There Yet?

Abstract

Magnetic resonance (MR) imaging is expected to play a key role in evaluating the outcome of clinical trials based on stem cell therapy. In order to facilitate and implement the translation of these therapies into the clinic, it will be necessary to monitor the immediate cellular engraftment, subsequent biodistribution and migration, and cell survival and differentiation non-invasively over time. This information is simply not obtainable by invasive biopsy procedures that not only just provide a limited histological “snapshot”, but may also be harmful for the patient.

MRI cell tracking, with its superior spatial resolution and excellent soft tissue anatomical detail, is now emerging as the technique of choice to monitor in real-time image-guided cell delivery and engraftment. Up until now, 10 clinical MRI cell tracking studies have been published, either using superparamagnetic iron oxide nanoparticles (SPIO) for proton (¹H) or perfluorocarbons for fluorine (¹⁹F) MRI. SPIOs create strong local magnetic field disturbances that spoil the MR signal leading to hypointense contrast, while the fluorinated compounds generate signal “hot spots” similar as those seen in nuclear medicine studies.

Twelve years ago, our Cellular Imaging Section in the Johns Hopkins Institute for Cell Engineering was part of the team that performed the first-in-man ¹H MRI SPIO-labeled cell tracking study. Previous imaging studies used ¹¹¹In-oxine (radio)labeled cells and ultra-sound guided local tissue injection. A major surprise, and only revealed by MRI, was that the cells missed their target in half the patients. Our second clinical ¹H MRI SPIO-labeled stem cell tracking study in patients with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) showed that systemically and intrathecally injected mesenchymal stem cells (MSCs) homed into neuroinflammatory lesions in the brain and spinal cord, where they act as immunomodulators.

Together with Q Therapeutics Inc. and Dr. Nicholas Maragakis in Neurology we are now collecting pre-IND data for performing a clinical ¹⁹F MRI tracking study of glial-restricted precursor cells in ALS. Lastly, funded by the Maryland Stem Cell Research Fund under the direction by Dan Gincel, we just obtained IND approval for a first-in man trial on ¹⁹F MRI of perfluorocarbon-labeled stromal vascular fraction (SVF) cells for treatment of radiation-induced fibrosis in women with breast cancer. Together with CelSense Inc. and Dr. Ricardo Rodriguez at CosmeticSurg LLC, we will be scanning the first patients by the end of this year (NCT02035085).