Exposure to Sulfur Hexafluoride Influences Viability in Cell Transplant Suspensions

Abstract

Cell transplantation is often performed with ultrasonographic guidance for accurate delivery through injection. In such procedures, using ultrasonographic contrast greatly improves target delivery. However, accumulating evidence suggests that exposure to such contrast agents may have negative effects on transplanted cells. No study so far has researched this issue. Stabilized sulfur hexafluoride (SF6) microbubbles are a widely used sonographic contrast agent. Skin hCD55 porcine transgenic fibroblasts and mesenchymal stem cells from human bone marrow (hMSCs) were exposed in vitro to SF6 in concentrations ranging from 1.54 µM to 308 µM. The effects on viability and cell growth were registered using an impedance-based label-free Real-Time Cell Analyzer (RTCA). Data was recorded every 15 min for 50 h of total study time. Both cell lines behave distinctly when exposed to SF6. Porcine fibroblast growth showed relevant alterations only when exposed to higher concentrations. In contrast, hMSCs showed progressive growth decrease in relation to SF6 concentration. Taken together, while SF6-based contrast agents pose no threat to patient safety, our results indicate that exposure of suspended stem cells to the contrast agent could affect the effective dose administered in cell therapy procedures. This prompts specific cell lineage testing, adjusting methods and properly compensating for cell loss, with a potential impact on procedural cost and success rates.