TY - JOUR

T1 - Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected (111)In-labeled human mesenchymal stromal cells

AU - Lyngbæk, Stig

AU - Ripa, Rasmus Sejersten

AU - Haack-Sørensen, Mandana

AU - Cortsen, Annette

AU - Kragh, Linda

AU - Andersen, Claus B

AU - Jørgensen, Erik

AU - Kjær, Andreas

AU - Kastrup, Jens

AU - Hesse, Birger

PY - 2009

Y1 - 2009

N2 - This pilot trial aimed to investigate the utilization of (111)In-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 (111)In-tropolone. Ten female pigs were included. The labeled cells were transplanted intramyocardially using a percutaneous injection system. The (111)In 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 (111)In accumulations up to 6 days after injection (N = 4). No MSC could be identified with FISH, and microscopy identified widespread acute inflammation. Focal (111)In accumulation, inflammation but no human MSC were similarly seen in pigs (N = 2) after immunosuppression. A comparable retention of (111)In activity was observed after intramyocardial injection of (111)In-tropolone (without cells) (N = 2), but without sign of myocardial inflammation. Injection of labeled non-viable cells (N = 1) also led to high focal (111)In 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 (111)In stays in the myocardium despite possible disappearance of labeled cells. This questions the clinical use of (111)In-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.

AB - This pilot trial aimed to investigate the utilization of (111)In-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 (111)In-tropolone. Ten female pigs were included. The labeled cells were transplanted intramyocardially using a percutaneous injection system. The (111)In 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 (111)In accumulations up to 6 days after injection (N = 4). No MSC could be identified with FISH, and microscopy identified widespread acute inflammation. Focal (111)In accumulation, inflammation but no human MSC were similarly seen in pigs (N = 2) after immunosuppression. A comparable retention of (111)In activity was observed after intramyocardial injection of (111)In-tropolone (without cells) (N = 2), but without sign of myocardial inflammation. Injection of labeled non-viable cells (N = 1) also led to high focal (111)In 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 (111)In stays in the myocardium despite possible disappearance of labeled cells. This questions the clinical use of (111)In-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.

U2 - 10.1007/s10554-009-9532-4

DO - 10.1007/s10554-009-9532-4

M3 - Journal article

C2 - 19921546

JO - International Journal of Cardiovascular Imaging

JF - International Journal of Cardiovascular Imaging

SN - 1569-5794

ER -