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

Abstract

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.

Magnetic-targeting of polyethylenimine-wrapped iron oxide nanoparticle labeled chondrocytes in a rabbit articular cartilage defect model

“…PEI/IONs were kindly provided by Professor Hua Ai (National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China). As described in previous studies, 5,11 Fe 3 O 4 nanocrystals with hydrodynamic diameter of 9 ± 2 nm was prepared by mixing Fe(acac) 3 (1 mmol) with 1,2-hexadecanediol (5 mmol), oleic acid (3 mmol), and oleylamine (3 mmol) in benzyl ether (10 ml) under nitrogen. Followed by heating to reflux (300 °C) for 1 h and cooling to RT.…”

Nanotechnology and Osteoarthritis. Part 1: Clinical landscape and opportunities for advanced diagnostics

“…Magnetic NPs are also used to track chondrocytes in order to monitor growth, differentiation, and regeneration in osteochondral defect repair. Labeling human derived MSCs and chondroprogenitor cells with SPIONs does not hinder cell viability, MSC marker expression, or chondrocyte differentiation 46,47 . Similarly, the SPION‐labeling process does not adversely affect the phenotype or viability of chondrocytes or the production of major cartilage matrix constituents in vitro or in vivo 46,53‐55 .…”

“…Tracking transplanted stem cells longitudinally in time and space enables non‐invasive monitoring of cell delivery, bio‐distribution, migration, survival, and tissue integration 46 . To enhance target cell uptake of SPIONs to detectable levels for MRI applications, cationic compounds, such as PLL, protamine sulfate, lipofectamine, and polyethylenimine (PEI) are used to produce cationic SPION complexes that electrostatically attach to the anionic cell membranes 47,48 . In an ex vivo model of human osteochondral fragments, possessing a central cartilage defect, human bone marrow MSCs labeled with SPIONs accumulate in the defect target region as followed by a T2‐weighted MRI (Figure 4).…”

“…Using T 2 or T 2 * MRI sequences, SPION‐labeled cells appear as a hypo‐intensity after injected in an OA joint model, do not impair hBMSC secretion profiles, and enable accurate visualization by MRI using a porcine knee model 51 . PEI‐wrapped SPION–labeled bone marrow‐derived mesenchymal stem cells, reported by Chen et al, 47 enable stem cell identification in repaired articular cartilage in a minipig model. To improve uptake efficiency, Pang et al 52 describe surface neutral ganglioside GD2 modified SPIONs, as neutral ganglioside GD2 is highly expressed on the surface of MSCs.…”

“…To enhance target cell uptake of SPIONs to detectable levels for MRI applications, cationic compounds, such as PLL, protamine sulfate, lipofectamine, and polyethylenimine (PEI) are used to produce cationic SPION complexes that electrostatically attach to the anionic cell membranes. 47,48 In an ex vivo model of human osteochondral fragments, possessing a central cartilage defect, human bone marrow MSCs labeled with SPIONs accumulate in the defect target region as followed by a T2-weighted MRI (Figure 4). 49 To minimize dose-dependent toxic effects on MSCs by the uptake of SPIONs, Markides et al 50 as a hypo-intensity after injected in an OA joint model, do not impair F I G U R E 3 A, Basic mechanism for simultaneous use of three cartilage permeable/impermeable contrast agents.…”