Quantitative CT and 19F-MRI tracking of perfluorinated encapsulated mesenchymal stem cells to assess graft immunorejection
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Peripheral artery disease (PAD) affects 12–14% of the world population, and many are not eligible for conventional treatment. For these patients, microencapsulated stem cells (SCs) offer a novel means to transplant mismatched therapeutic SCs to prevent graft immunorejection. Using c-arm CT and 19F-MRI for serial evaluation of dual X-ray/MR-visible SC microcapsules (XMRCaps) in a non-immunosuppressed rabbit PAD model, we explore quantitative evaluation of capsule integrity as a surrogate of transplanted cell fate.
Materials and methods
XMRCaps were produced by impregnating 12% perfluorooctylbromine (PFOB) with rabbit or human SCs (AlloSC and XenoSC, respectively). Volume and 19F concentration measurements of XMRCaps were assessed both in phantoms and in vivo, at days 1, 8 and 15 after intramuscular administration in rabbits (n = 10), by 3D segmenting the injection sites and referencing to standards with known concentrations.
XMRCap volumes and concentrations showed good agreement between CT and MRI both in vitro and in vivo in XenoSC rabbits. Injected capsules showed small variations over time and were similar between AlloSC and XenoSC rabbits. Histological staining revealed high cell viability and intact capsules 2 weeks after administration.
Quantitative and non-invasive tracking XMRCaps using CT and 19F-MRI may be useful to assess graft immunorejection after SC transplantation.
KeywordsQuantitative tracking 19F-MRI Encapsulated stem cells Peripheral artery disease Immunorejection
Fluorine magnetic resonance imaging
Analysis of variance
Balanced steady-state free precession
Digital subtraction angiogram
Field of view
Hematoxylin and eosin
Anti-human nuclear antigen
Maximum intensity projection
Mesenchymal stem cells
Peripheral artery disease
Region of interest
Superficial femoral artery
Supported by a grant from Siemens AG, National Heart, Lung, and Blood Institute (NIH R33-HL089029), and the Maryland Stem Cell Research Foundation (2008-MDSCRFII-0399).
GW was responsible for acquiring imaging data, image processing algorithm development, statistical analysis, result interpretation, and drafting the initial manuscript. YF was responsible for XMRCaps production, animal model preparation, imaging acquisition, histopathology, and drafting the final manuscript. SMS assisted with study design, MR imaging sequence tuning, and manuscript preparation. SSH assisted with study design, coil tuning, and manuscript preparation. DLK was responsible for study conception design, animal model preparation, image acquisition, interpretation, critical review, and drafting the final manuscript.
Compliance with ethical standards
Conflict of interest
DLK has received research grants from Siemens AG and BTG plc. SMS is a former employee of Siemens Healthcare.
All animal studies were approved by the Institutional Animal Care and Use Committee.
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