MRI is expected to play a key role in evaluating the outcome of clinical trials based on stem and immune 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.
MRI is expected to play a key role in evaluating the outcome of clinical trials based on stem and immune 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, the 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. We recently 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. We will be scanning the first patients this year (NCT02035085). At present, clinical cell tracking trials have only provided information on immediate cell delivery and short-term cell retention. The next big question is if these cell tracking tools can improve the clinical management of our patients and if so, by how much, for how many and for whom, and if we need to track therapeutic cells in every patient. To become clinically relevant, we now have to demonstrate how cell tracking techniques can inform patient management and affect clinical outcomes.
Learning objectives:
1) To learn about the currently available, clinically applicable cell tracking/imaging techniques. There are two ways of making cells detectable: labeling cells with exogenous nanoparticles or endogenous cellular expression of reporter genes.
2) To learn how cell tracking can aid in optimizing the practice of clinical cell therapy. This includes conducting image-guided cell injections, visualization of cell homing and migration, and assessment of cell survival.
3) To learn about a first-in-man clinical trial on tracking cells using fluorine-based magnetic resonance imaging and the key steps that were involved for obtaining clinical approval.