257 A novel polysaccharide-based porous scaffold for cell delivery into the infarcted heart

BackgroundCellular cardiomyoplasty has been proposed as an attractive strategy to repair myocardial damage. One of the crucial point is the optimal delivery strategy. In the present study, we examined the use of an implantable porous scaffold for promoting bone marrow-derived mesenchymal stem cells (MSCs) survival and functions in a rat model of acute myocardial infarction.Methods and ResultsCardiac patch was based on biodegradable polysaccharides porous scaffold. After ligation of the left anterior coronary artery, the fate of 1x106 GFP+ MSC administered either using cellularized scaffold implantation or direct injection was examined at 1 and 2 months. The number of residual GFP+ cells in the sample studied was estimated on the basis of the fluorescence emitted by a defined number of GFP+ cells used for calibration. Cellularized scaffold allowed a more efficient delivery and the difference with direct injection was significant at 2 months, with respectively 2100±1300×103 and 215±85x103 residual GFP+ cells (p<0.03). Cardiac tissue levels of matrix metalloproteinase-2 and -9 mRNA were similar whatever the administration conditions but a slight increase in the local production of vascular endothelial growth factor was observed at 2 months after patch implantation in comparison to direct injection (p<0.05). In animals having received MSC implemented on scaffold, clusters of GFP+ cells, mainly phenotypically consistent with immature MSC cells, were detected in the peri-infarct area. The increased survival using scaffold was not translated in an improved myocardial remodelling and functions with no significant difference in the LVEDD, LVESD, and FS between the 2 groups as in comparison with animals implanted with non cellularized scaffold.ConclusionsThese findings demonstrate that the implantation of cellularized grafts is safe and effective for delivering mesenchymal stem cells into damaged myocardium, and results in a better cellular engraftment compared to direct injection