Magnetic Resonance Fluoroscopy Allows Targeted Delivery of Mesenchymal Stem Cells to Infarct Borders in Swine

Abstract

Background-The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype.MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately. Methods and Results-A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7ϫ3.3ϫ8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem. Conclusions-Precise

Percutaneous methods of vector delivery in preclinical models

“…25,26 Other imaging modalities as cardiac MRI scanners in conjunction with specialized catheters have been used as well to establish endomyocardial delivery of agents. 27 Other studies evaluated the capacity of ultrasound-targeted microbubble destruction to deliver viral vectors successfully delivering VEGF and SCF genes into the infarcted heart in mice. 28 Moreover, access can be realized by a special catheter that is advanced into the coronary sinus and target either the myocardium or coronary artery.…”

Cell vehicle targeting strategies

“…In some cases current technological advancements allow diseased areas to be mapped, allowing guided instruments apply therapeutic cells directly to the diseased spot such as heart infarction. 25 Instrument-guided devices allow cell introduction to be feasible for a range of target organs, including heart, trachea, lung and brain.…”

Regenerative therapies in electrophysiology and pacing

“…These include transfection in vitro with either fluorescent [31] or nonfluorescent [60] proteins, the use of fluorescence in situ hybridization (FISH) to identify delivered cells by their chromosomal content (usually by delivering male cells to a female host) [61], the use of species-specific surface markers to identify delivered cells in a xenographic host [31,36] (see Fig. 4), and labeling cells with inorganic particles such as Feridex [62,63] or radiotracers [64][65][66].…”