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MRI and CT tracking of mesenchymal stem cells with novel perfluorinated alginate microcapsules
Journal of Cardiovascular Magnetic Resonance volume 12, Article number: O14 (2010)
Background and objectives
Stem cell therapies, although promising for treating ischemic arterial diseases, suffer from poor engraftment and the inability to noninvasively monitor and track transplanted cells in vivo. Stem cell microencapsulation in conjunction with an imaging contrast agent provides a means to prevent cell immunorejection and enable cell tracking with appropriate imaging modalities. The objective of this study was to design and evaluate a novel MRI- and CT-visible, immunoprotectable alginate microcapsule containing an imaging contrast agent, perfluorooctylbromide (PFOB), for mesenchymal stem cell (MSC) delivery.
Microencapsulation of bone marrow-derived rabbit MSCz (1.5 × 106cells/ml) was performed using a modified cell microencapsulation method with the addition of PFOB. MSCs viability was determined using a fluorometric assay. In vitro phantom studies using 19F MRI and c-arm CT imaging were performed to determine the minimum detectable number of PFOB Caps using standard clinical imaging systems. New Zealand White (NZW) rabbits (n = 16) were randomized to receive 6 injections (~500 capsules/injection) of unlabeled microcapsules, PFOB Caps, or naked MSCs in the medial thigh. X-ray angiograms, c-arm CT, and 19F MR images were taken within 1-14 days after injection in a rabbit PAD model. Intensity-weighted centroids of each injection site from CT images and postmortem 3D rendering volumes were determined after coregistration using 3D registration software (Dextroscope). Registration error was quantified by linear distance between paired CT and postmortem injection sites.
The viability of rabbit MSCs encapsulated with PFOB was 90 ± 3% immediately after encapsulation and remained high (88 ± 5% at 4 weeks post-encapsulation). As few as 2 and 5 PFOB microcapsules could be detected in phantoms using c-arm CT and 19F MRI, respectively. In vivo visualization of PFOB microcapsules with c-arm CT images was confirmed in 95% of the injections whereas unlabeled capsules could not be detected (Fig 1A). PFOB microcapsule injections remained detectable by MRI and CT up to 2 weeks post-injection. Using 19F MRI, transplanted PFOB microcapsules in rabbit medial thigh were demonstrated 100% correspondence to the injection location on c-arm CT (Fig 1A, B). In the coregistered volumes, the mean offset between centers of mass at each injection site was 2.83 ± 0.85 mm (Fig 1C).
PFOB microcapsules provide an ideal microenvironment for maintaining MSC viability in vitro, while enabling the monitoring of MSC delivery and tracking of engraftment in vivo using clinical MRI and CT imaging systems.
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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Fu, Y., Xie, Y., Kedziorek, D.A. et al. MRI and CT tracking of mesenchymal stem cells with novel perfluorinated alginate microcapsules. J Cardiovasc Magn Reson 12 (Suppl 1), O14 (2010). https://doi.org/10.1186/1532-429X-12-S1-O14
- Mesenchymal Stem Cell
- Medial Thigh
- Imaging Contrast Agent
- Alginate Microcapsule
- Cell Microencapsulation