Medical imaging of superparamagnetic iron oxide nanoparticle-labeled stem cells: a review on tracking strategies for regenerative medicine

Stem cell-based therapies have substantial potential in regenerative medicine, but their translation depends in part on reliable, non-invasive assessment of transplanted-cell localization and fate. Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely used to label stem and stromal cells for imaging. This structured narrative review, informed by a systematic PubMed literature search, examines the imaging strategies used for SPION-labeled stem-cell tracking and the signal mechanisms underlying multimodal approaches. The modality-specific searches retrieved 218 records; removal of 16 duplicate records left 202 unique publications for relevance assessment. Evidence was synthesized at the study level rather than using search yields as denominators. MRI was the principal modality for direct visualization of SPIO-labeled cells, although susceptibility-related blooming, label dilution, extracellular iron, and uptake by host phagocytes complicate quantitative interpretation and assessment of cell viability. CT and micro-CT had limited roles in direct cell tracking and were used mainly for complementary anatomical or structural assessment. Conventional and focused ultrasound were used predominantly for guidance, delivery, or assistance with labeling, whereas MSOT can provide optical cell-tracking contrast when an appropriate optically absorbing construct is used. PET and SPECT detect radionuclide emissions or reporter-derived signals rather than magnetic SPIO signal; when a radionuclide is physically linked to an SPIO construct, the nuclear signal may report that radiolabeled construct but remains emission-based. Magnetic particle imaging (MPI) directly detects SPIO and offers tracer-specific quantitative potential, although clinical availability remains limited. Future translation requires rigorous signal attribution, standardized nanoparticle and labeling characterization, validation of cell-function preservation, improved longitudinal quantification, and harmonized regulatory and manufacturing frameworks.