Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected 111In-labeled human mesenchymal stromal cells

This pilot trial aimed to investigate the utilization of In-111-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with In-111-tropolone. Ten female pigs were included. The labeled cells were transplanted intramyocardially using a percutaneous injection system. The In-111 activity was determined using gamma camera imaging. Excised hearts were analyzed by fluorescence in situ hybridization (FISH) and microscopy. Gamma camera imaging revealed focal cardiac In-111 accumulations up to 6 days after injection (N = 4). No MSC could be identified with FISH, and microscopy identified widespread acute inflammation. Focal In-111 accumulation, inflammation but no human MSC were similarly seen in pigs (N = 2) after immunosuppression. A comparable retention of In-111 activity was observed after intramyocardial injection of In-111-tropolone (without cells) (N = 2), but without sign of myocardial inflammation. Injection of labeled non-viable cells (N = 1) also led to high focal In-111 activity up to 6 days after intramyocardial injection. As a positive control of the FISH method, we identified labeled cells both in culture and immediately after cell injection in one pig. This pilot trial suggests that after intramyocardial injection In-111 stays in the myocardium despite possible disappearance of labeled cells. This questions the clinical use of In-111-labeled cells for tracking. The results further suggest that xenografting of human MSC into porcine hearts leads to inflammation contradicting previous studies implying a special immunoprivileged status for MSC.