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Radiology. 2019 Jul;292(1):129-137. doi: 10.1148/radiol.2019182176. Epub 2019 May 7.

Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI.

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From the Department of Radiology and Molecular Imaging Program at Stanford (MIPS) (A.J.T., H.N., O.L., K.Y., K.L., L.K., C.W., T.L., H.E.D.), Department of Comparative Medicine (S.F.), and Department of Pediatrics (H.E.D.), Stanford University School of Medicine, 725 Welch Rd, Room 1665, Stanford, CA 94305-5654; Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany (A.J.T.); and Department of Orthopedics and Sportorthopedics, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany (L.K., J.T., R.B.).


Background Cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair. Purpose To determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model. Materials and Methods Between January 2016 and December 2017, 10 Göttingen minipigs (n = 5 male; n = 5 female; mean age, 6 months ± 5.1; age range, 4-20 months) received implants of unlabeled (n = 12) or ferumoxytol-labeled (n = 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0-100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation. Results Ferumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8; P < .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P > .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3; P = .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12-24 weeks. Conclusion Ferumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model.


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