High-precision in vivo tracking of stem cells using carbon-14 labeling: a novel quantitative approach for assessing therapeutic efficacy and safety

Accurate long-term tracking of transplanted stem cells is essential for evaluating therapeutic efficacy, biodistribution, and safety in regenerative medicine. Conventional imaging and molecular tracing methods often lack the sensitivity or temporal stability required for quantifying small residual cell populations over extended periods. Carbon-14 (C-14), a long-lived radioactive isotope, offers a unique opportunity to overcome these limitations by enabling durable and quantitative labeling of stem cells. C-14 labeling provides an inheritable molecular marker that is stably incorporated into nucleic acids and other macromolecules, permitting attomole-level detection using accelerator mass spectrometry (AMS). This analytical sensitivity enables reliable quantification of fewer than 100 transplanted cells within complex host tissues—an order of magnitude beyond the detection limits of polymerase chain reaction (PCR) and other conventional assays. Through AMS-based analysis of time-resolved tissue samples, C-14 tracing supports precise assessment of cell survival, migration, engraftment, and long-term persistence. The approach further allows the identification of adverse outcomes such as ectopic engraftment, uncontrolled proliferation, or tumorigenicity by detecting abnormal expansion or mislocalization of labeled cell populations. Collectively, C-14-based tracking provides both quantitative accuracy and temporal resolution suitable for rigorous preclinical evaluation of stem cell therapies. C-14 tracing represents a powerful analytical platform capable of transforming cell tracking strategies in regenerative medicine. Its unparalleled sensitivity and long-term detection capability offer clear advantages for studying stem cell fate, optimizing therapeutic protocols, and strengthening safety assessments. Continued methodological refinement and broader standardization will be crucial for translating this technology into wider preclinical and clinical use.