In Vivo MRI Tracking of Polyethylenimine-Wrapped Superparamagnetic Iron Oxide Nanoparticle–Labeled BMSCs for Cartilage Repair: A Minipig Model

OBJECTIVE: To evaluate the feasibility of tracking polyethylenimine (PEI)-wrapped superparamagnetic iron oxide (SPIO) nanoparticle–labeled, bone marrow–derived mesenchymal stem cells (BMSCs) by in vivo magnetic resonance imaging (MRI) in articular cartilage repair in a minipig model. METHODS: Eighteen Guizhou minipigs were randomly divided into three groups (groups A, B, and C). In group A, PEI-wrapped SPIO nanoparticle (PEI/SPIO) and green fluorescent protein (GFP) colabeled, autologous BMSCs seeded in type II collagen gel were transplanted into the articular cartilage defects of the minipig model. In group B, GFP-labeled, autologous BMSCs seeded in type II collagen gel were transplanted. In group C, no treatment was applied for cartilage defects. All minipigs underwent clinical 3.0-T MR imaging at 4, 8, 12, and 24 weeks postsurgery. The findings were compared histologically. RESULTS: Prussian staining and transmission electron microscope showed that BMSCs were efficiently labeled by PEI/SPIO. Cell viability, proliferation, and differentiation were comparable between labeled and unlabeled cells. MRI SET2WI sequence revealed that marked hypointense signal void areas representing the transplanted labeled BMSCs could be observed for at least 24 weeks. Histochemical staining confirmed the presence of Prussian blue–positive cells and GFP-positive cells at the hypointense signal void areas. At 24 weeks postsurgery, both MR signals and histologic staining of minipigs in groups A and B at the cartilage defect were close to the normal cartilage. CONCLUSIONS: 3.0-T MRI in vivo tracking of PEI/SPIO-labeled BMSCs seeded in type II collagen gel on cartilage repair following transplantation is feasible in minipigs.