Clinical imaging in regenerative medicine

Abstract

In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring.

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

“…Reduction of extracellular NPs is essential for the correct interpretation of downstream cell toxicity assays 66,67 and for improving MRI single-cell detection, because extracellular NPs will be most probably lost during cell migration.…”

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…The most commonly used methods are summarized in Table 2 and have been thoroughly reviewed in studies by Kircher et al, 9 Hong et al, 21 Naumova et al, 22 James and Gambhir, 34 Chen et al, 35 and Zhang et al 36 For preclinical or clinical studies, it is essential to consider the advantages and disadvantages of each molecular imaging modality. The challenge is to develop effective imaging strategies with a combination of imaging modalities, labeling reporter systems, and probes.…”

“…SPIONs, fluorescent dyes, or radionuclides can be used as probes to directly prelabel stem cells for noninvasive tracking. 9,[21][22][23] Standardized protocols used for labeling stem cells with SPIONs were previously compiled by us, 15,24 and other direct-labeling reagents were reviewed by Marks and Nolan 25 and Progatzky et al 26 Indirect labeling is a considerably different method, which includes genetic modification in order to either produce an appropriate signal-generating molecule or increase the affinity of cells to contrast agents. 9,21,[27][28][29][30][31][32] Transient expression of reporter proteins by DNA vector transfection is often included in this set of cell labeling.…”

Gaining Mechanistic Insights into Cell Therapy Using Magnetic Resonance Imaging

“…Indeed, cell therapy in a clinical setting is likely to require the use of diagnostic imaging to define patients who will benefit from the intervention and also to guide and monitor the effects of cell therapy. Clinical imaging techniques, such as computer tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI), have all been incorporated in early translational trials [8]. For instance, PET imaging of dopaminergic receptor binding has been crucial to demonstrate the functional activity of fetal tissue transplants in animal models [9], as well as patients with Parkinson's disease [10].…”