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

Abstract

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.

Transendocardial cell injection is not superior to intracoronary infusion in a porcine model of ischaemic cardiomyopathy: a study on delivery efficiency

“…4 weeks after MI) whereas others performed cell delivery within 7 days after acute MI. In addition, we used autologous MSC in contrast to allogeneic or human MSC ,thereby preventing an immunological response or ectopic tissue formation [21][22][23]. Until now, no study determined MSC retention via nuclear imaging in an ischaemic cardiomyopathy model using the NOGA electronic mapping system, which allows accurate injection by identifying the area of MI and border zone without fluoroscopic guidance [24].…”

Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

“…While 111 In provides a longer time window for cell imaging, 99m Tc can be used in higher doses to improve short-term imaging resolution. Several groups have used 111 In to image in vivo trafficking and biodistribution of MSCs around sites of myocardial injury in the canine 39, 40 and porcine animal models 41. Human clinical studies have also used 111 In-oxine 31, 42, 43 and 99m Tc-Hexamethylpro­pleneamine oxine 44-46 to assess stem cell trafficking in acute and chronic myocardial infarction.…”

Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: a clinical perspective

“…Cell imaging with SPECT or PET has been implemented in a number of preclinical studies to address key questions concerning the efficiency of cell retention for different cell types and delivery techniques [18, 26, 68, 106, 107]. Early rodent studies shed light on the initial homing of cells to the infarcted myocardium after systemic delivery and the temporal profile of their distribution to the lungs followed by the liver, kidneys and spleen [100, 106].…”