Magnetic particle imaging reveals microenvironment-driven retention of SPIO-labeled MSCs and enables CXCR3 engineering to enhance antifibrotic therapy

Mesenchymal stromal cell (MSC) transplantation holds great promise for treating liver fibrosis; however, the “black box” of their in vivo fate—specifically their biodistribution, survival, and clearance kinetics—remains a critical barrier to clinical translation. To address this challenge, we established a longitudinal cell-tracking framework using Magnetic Particle Imaging (MPI) with superparamagnetic iron oxide (SPIO) nanoparticles to decipher the behavior of bone marrow-derived MSCs (BMSCs) in liver fibrosis models. We demonstrated that MPI provides a highly sensitive, background-free readout of SPIO-associated cell tracer burden, revealing that the fibrotic microenvironment significantly prolongs BMSC-associated tracer retention compared with healthy controls. Mechanistic investigation identified the upregulation of the chemokine CXCL10 in the fibrotic liver as a key driver for this retention. Leveraging this insight, we engineered CXCR3-overexpressing BMSCs to enhance chemotactic responsiveness. Longitudinal MPI tracking confirmed that CXCR3 engineering significantly augmented early hepatic homing and sustained long-term retention of SPIO-labeled cells. Importantly, this enhanced “cell exposure” directly translated into superior therapeutic outcomes. Collectively, our work establishes MPI as a robust nanobiotechnology platform for linking cell-associated retention kinetics with therapeutic benefit in deep tissues, and validates a microenvironment-guided engineering strategy to boost the efficacy of MSCs for chronic liver disease.