Mesenchymal stem cell (MSC) transplantation offers an alternative strategy for therapeutic angiogenesis for the management of ischemic cardiovascular disease. However, the poor survival of transplanted cells and lack of sustained engraftment severely limits therapeutic efficacy. We propose a novel cell microencapsulation method utilizing perfluoro-octyl-bromide (PFOB) impregnated alginate-poly-L-lysine-alginate microcapsules (PFOB Caps) that enable noninvasive cell delivery and tracking using conventional clinical X-ray fluoroscopy. Microen-capsulation of rabbit MSCs (1x10
6
cells/ml) combined with PFOB-loaded alginate was performed with an electrostatic droplet generator. Control capsules lacked PFOB. MSC viability post-encapsulation was determined using a microfluorometric assay. X-ray fluoroscopy was performed during direct intramuscular/intramyocardial injection of 2300 capsules/injection in a rabbit peripheral arterial disease (PAD) model (n=2) and a swine reperfused myocardial infarction (MI) model (n=3). Fluoroscopy and angiographic computed tomography (DynaCT) were performed to assess the ability to monitor microcapsule delivery and tracking with X-ray. As compared to control capsules, PFOB Caps showed similar swelling, when subjected to 55 mM sodium citrate incubation (mean diameter increased 5.4% for PFOB vs. 4.5% for control, P=NS), and mechanical strength (broken capsules from osmotic pressure tests: 2/591 for PFOB and 2/603 for control). The PFOB Caps showed a small viability decrease immediately after encapsulation (90±3%) with no significant further viability loss up to 4 weeks
in vitro
(79±5%). In both PAD and MI animals, successful injection of PFOB Caps could be demonstrated with DynaCT but not with real-time fluoroscopic images. Control capsules were never detected. CT tracking of PFOB Caps was possible up to 5 weeks post-injection. PFOB microcapsules provide an ideal microenvironment for maintaining MSC viability
in vitro
. In addition, PFOB proves to be a non-toxic, radiopaque agent suitable for cell tracking using conventional fluoroscopy
in vivo
. PFOB microencapsulation of MSCs may be a novel approach for X-ray tracking therapeutic angiogenesis.
In Vivo Mesenchymal Stem Cell Tracking with PET Using the Dopamine Type 2 Receptor and 18F-Fallypride