Whole-Body in Vivo MPI Cytometry Reveals Injection Route-, Dose-, Cell Size- and Disease-Dependent Differences in Organ Biodistribution

Robust quantification of the whole-body biodistribution of cellular therapeutics remains a major challenge. We performed in vivo cytometry using magnetic particle imaging (MPI) to track magnetically labeled cells on a time scale of minutes with high sensitivity, zero background signal, and simple linear quantification. Human mesenchymal stem cells (hMSCs, ∼25 µm) and human neural precursor cells (hNPCs, ∼10 µm) were labeled with superparamagnetic iron oxide nanoparticles, and mapped with MPI after intravenous (IV) or intra-arterial (IA) injection in normal mice. The tissue site and numbers of cell accumulation and retention were dependent on cell size, cell dose, injection frequency and injection route, with the lung and liver serving as the major entrapment organs. In mice with experimental autoimmune encephalomyelitis, but not in normal mice, hMSCs also homed to the spleen. Integrating MPI cytometry with cell therapy may aid in further optimization of the route, dose, and frequency of cell administration.