Image Guided Evaluation of Cellular Retention and Survival After Intramyocardial Transcatheter Based Mesenchymal Stem Cell Transplantation Into the Infarcted Pig Heart

Purpose: Cardiac cell therapy represents as a promising concept for the failing heart. However, while several delivery methods exist, the overall low retention and survival within the heart remains a major issue and numerous studies suggest a high washout particularly in the early phase after transplantation. We investigate the efficacy of transcatheter-guided, intramyocardial transplantation of mesenchymal stem cells (MSCs) in a translational porcine myocardial infarction model with particular regards to retention and survival. Methods: Allogenic porcine MSCs were characterized and labelled with iron-oxide micro-particles (MPIOs). Next, eight pigs (30-35kg) with chronic MI underwent 3D NOGA mapping-guided, transcatheter intramyocardial transplantation of 1.5x107 MSCs into the anterior-septal wall of the MI border-zone. Thereafter in-vivo cell-tracking was performed using MRI, before the hearts were harvested at different time-points (1, 3, 6, 12 and 24hours) post transplantation for post-mortem assessment. According to the 3D NOGA injection-map, tissue-samples were taken to undergo a combined MACS/FACS cell-separation approach and immunohistochemistry (IHC) to determine cell retention and survival. Results: Transplantation was successful in all animals and MRI displayed the transplanted MPIO-labelled MSCs in the anterior-septal wall (corresponding to the injection sites). At all time-points, viable MSCs could be isolated from the heart and combined MACS/FACS separation (purity up to 98%) revealed up to 11.4% of the injected MSCs (mean: 5.2±4.1%) in the respective samples. IHC further verified intramyocardial presence via positive staining for MSC-specific markers and anti-FITC targeting the MPIOs. The cells appeared to be integrated and could be detected in clusters or in the interstitial areas. Conclusion: This study provides important insights into the early efficacy of transcatheter guided intramyocardial MSC transplantation in a translational animal model. Although the overall retention appears to be relatively low, these data confirm cell survival in the early phase after transplantation. Further optimization of delivery strategies and cell application formats is mandatory to improve intramyocardial retention and survival in future cell therapy concepts.