Image-guided <em>In Vivo</em> Tracking of Transplanted Distal Lung Epithelial Progenitor Cells for Pulmonary Fibrosis Using Magnetic Particle Imaging

Pulmonary fibrosis (PF) is a progressive and chronic lung disease characterized by repeated alveolar epithelial injury that leads to excessive extracellular matrix deposition, resulting in tissue thickening, scarring, and impaired gas exchange, leading to respiratory dysfunction. In the United States, around 50,000 new cases are reported annually, with patients facing serious complications such as pneumothorax, pulmonary hypertension, respiratory failure, and an increased risk of lung cancer. Current therapeutic options are limited in efficacy and primarily aim to slow disease progression. Cell therapy has emerged as a promising intervention, offering the potential to regenerate damaged lung tissue, modulate inflammation, and improve pulmonary function. However, the effectiveness of these therapies depends significantly on the ability to monitor the distribution, survival, and integration of transplanted cells within the host lungs. Magnetic Particle Imaging (MPI) is a novel, non-invasive, preclinical imaging modality that utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as tracers. MPI offers high sensitivity, specificity, and no background signal, allowing for real-time and quantitative tracking of labeled cells in vivo. In this study, we investigated the use of MPI for monitoring human distal lung epithelial progenitor cells transplanted into the lungs of immunocompromised mice. Cells were labeled with varying SPION concentrations to optimize the signal, confirmed by immunostaining and iron quantification. After intratracheal instillation, 2D MPI scans were acquired to track the spatial distribution of transplanted cells. Longitudinal imaging over 2 weeks enabled visualization of cell integration and retention within lung tissue. Successful instillation exhibited MPI signals in both left and right lungs, which decreased (~65%) over time. Mice were subsequently sacrificed for histological validation. This study demonstrates the utility of MPI for noninvasive, longitudinal tracking of cell therapy in pulmonary fibrosis, and pivots around the intricate techniques utilized during the procedures.