Abstract
Magnetic cell delivery system, termed as magnetic targeting, has been developed for minimal invasive cell transplantation. Cells are magnetically labeled with nano-sized iron particles. However, the temporal change in iron particles in vivo has not been clarified. In addition, the influence of magnetic resonance imaging (MRI) after magnetic targeting therapy has never been investigated. In this study, magnetically labeled bone marrow mesenchymal stem cells (MSCs) were injected into rabbit knee joint with an articular cartilage defect, with or without existence of the magnetic field (m-MSC group and MSC group). Phosphate-buffered saline was injected as a control. Articular cartilage defects were assessed by MRI using a 4.7 Tesla magnet at 1, 4, and 12 weeks after treatment. Articular cartilage defects were also evaluated using Safranin-O staining, type II collagen immunostaining, and Berlin blue staining at 1, 4, and 12 weeks after treatment. In the assessment using T2 mapping of MRI, the area of repaired tissues with T2 had a value similar to that for articular cartilage. This was significantly larger in the m-MSC group than that in the other groups at 12 weeks after treatment. Histological findings by Safranin-O staining and type II collagen immunostaining also revealed better cartilage repair in the m-MSC group than in the other groups. T2 mapping of MRI was, therefore, considered to successfully reflect the degree of cartilage repair. In contrast, T2* images of MRI showed hypointense areas in cartilage defects in the m-MSC group. The T2* hypointense area in the m-MSC group was significantly larger than that in the other groups at 1 and 4 weeks, but not at 12 weeks after treatment. In the histological assessment, iron particles stained with Berlin blue could be detected in repaired tissues at 1 and 4 weeks, but not at 12 weeks after treatment. The T2* hypointense area seems to indicate the existence of iron particles. These findings suggest that MRI can evaluate the regenerative process of cartilage with magnetic targeting and kinetics of ferucarbotran after magnetic targeting of MSCs. MRI can be used safely without inhibiting the cartilage repair, after magnetic targeting of MSCs.
Impact Statement
This study is very important as a preclinical study of magnetic resonance imaging (MRI) assessment after magnetic targeting of mesenchymal stem cells. The findings of this study show that MRI is useful for evaluating the regenerative process of cartilage with magnetic targeting and kinetics of iron particles, and is less invasive without any complications.
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