Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging:: effect on cell proliferation and differentiation

Purpose: Stem cell therapy seems to be a new treatment option within cardiac diseases to improve myocardial perfusion and function. However, the delivery and traceability of the cells represent a problem. Radioactive labelling with In-111 could be a method for tracking mesenchymal stem cells (MSCs). However, In-111 could influence the viability and differentiation capacity of MSCs, which would limit its use. Therefore, the aim of this study was to evaluate the influence of In-111 labelling in doses relevant for SPECT imaging in humans on the viability and differentiation capacity of human MSCs. Methods and results: Human MSCs isolated from bone marrow were incubated with In-111-tropolone (15-800 Bq/cell). The labelling efficiency was approximately 25% with 30 Bq/cell In-111. The MSC doubling time was 1.04 +/- 0.1 days and was not influenced by In-111 within the range 15-260 Bq/cell. Using 30 Bq In-111/cell it was possible to label MSCs to a level relevant for clinical scintigraphic use. With this dose, In-111 had no effect on characteristic surface and intracellular markers of cultured MSCs analysed both by flow cytometry and by real-time polymerase chain reaction. Further, the labelled MSCs differentiated towards endothelial cells and formed vascular structures. Conclusion: It is possible to label human MSCs with In-111 for scintigraphic tracking of stem cells delivered to the heart in clinical trials without affecting the viability and differentiation capacity of the MSCs. This creates an important tool for the control of stem cell delivery and dose response in clinical cardiovascular trials.