- Moderated poster presentation
- Open Access
PET-MRI tracking of imaging-visible microencapsulated stem cells in immunocompetent rabbits
© Fu et al; licensee BioMed Central Ltd. 2013
- Published: 30 January 2013
- Thymidine Kinase
- Peripheral Arterial Disease Patient
- Medial Thigh
- Cell Microencapsulation
- Exogenous Stem Cell
Exogenous stem cell therapy has shown benefits for treating peripheral arterial disease patients, who are not amenable for conventional revascularization therapy. Previously, we have demonstrated the ability of imaging-visible cell microencapsulation to overcome the challenges of poor cell retention/survival and difficulties with monitoring cell delivery success. However, in vivo cell viability cannot be assessed noninvasively. Here, we investigate the potential of PET-MRI tracking of 19F MRI-visible microencapsulated human mesenchymal stem cells (hMSCs) labeled with triple-fusion (TF) reporter gene in non-immunosuppressed rabbits.
Bone marrow-derived hMSCs were stably transfected with a lentiviral vector encoding firefly luciferase, red fluorescence protein, and thymidine kinase. Alginate cell microencapsulation was performed using a modification to incorporate perfluorooctylbromide (PFOB). Bioluminescence imaging (BLI, Xenogen IVIS 2000) was acquired before and after cell encapsulation to assess in vitro cell viability. Rabbits received either intramuscular injection of PFOB-encapsulated TF-hMSCs in the medial thigh followed by intravenous administration of [18F] 9-[4-fluoro-3-(hydroxymethy) butyl] guanine ([18F]-FHBG) (n=7, 1.7±0.7 mCi), or PFOB-encapsulated TF-hMSCs that were pre-incubated with [18F]-FHBG (n=3, 55±2 µCi). Dynamic PET imaging (Siemens HRRT CPS Innovation) was acquired immediately or 60 min after transplantation for 30-90 min. Proton (3D GRE, TR/TE=15/5.45 ms, FOV=186x230 mm, voxel size=0.45x0.45x1.5mm) and 19F MRIs (TrueFISP, Siemens Tim Trio, TR/TE=4.1/2.0 ms, 32 averages, FOV=250x250 mm, image matrix=192x192, BW=1002 Hz/pixel, voxel size= 1.3x1.3x1.25 mm) were obtained 1-2 days after delivery. PET images were fused with 1H/19F MR to identify the location of transplanted cells. Follow-up PET imaging was repeated within 1-14 days with intravenous or ultrasound-guided intramuscular (0.7±0.3 mCi/thigh) of administration of [18F]-FHBG. Follow-up 19F MRIs were acquired 1-2 days after PET imaging. BLI was performed 2 weeks after delivery.
We demonstrate xenogeneic MSC delivery in non-immunosuppressed large animals using novel MRI-visible microencapsulation and reporter gene labeling. PFOB microencapsulation of TF-hMSCs enables cell tracking and viability assessment using clinical PET-MRI.
Funding support was provided by NIH R21/R33-HL89029 & MD-SCRFII-039
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.