Superparamagnetic Iron Oxide Nanoparticles Labeling of Bone Marrow Stromal (Mesenchymal) Cells Does Not Affect Their “Stemness”

Abstract

Superparamagnetic iron oxide nanoparticles (SPION) are increasingly used to label human bone marrow stromal cells (BMSCs, also called “mesenchymal stem cells”) to monitor their fate by in vivo MRI, and by histology after Prussian blue (PB) staining. SPION-labeling appears to be safe as assessed by in vitro differentiation of BMSCs, however, we chose to resolve the question of the effect of labeling on maintaining the “stemness” of cells within the BMSC population in vivo. Assays performed include colony forming efficiency, CD146 expression, gene expression profiling, and the “gold standard” of evaluating bone and myelosupportive stroma formation in vivo in immuncompromised recipients. SPION-labeling did not alter these assays. Comparable abundant bone with adjoining host hematopoietic cells were seen in cohorts of mice that were implanted with SPION-labeled or unlabeled BMSCs. PB+ adipocytes were noted, demonstrating their donor origin, as well as PB+ pericytes, indicative of self-renewal of the stem cell in the BMSC population. This study confirms that SPION labeling does not alter the differentiation potential of the subset of stem cells within BMSCs.

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…[94][95][96][97] We were able to obtain chondrogenic, osteogenic, and adipogenic differentiation of mesenchymal stem cells after SPION labeling. 15 More recently, Balakumaran et al 98 successfully demonstrated the potential of SPI-ON-labeled stem cells to appropriately differentiate in vivo. Figure 2 shows Feridex-labeled mesenchymal stem cells harvested from bone marrow of Wistar rats, which are differentiated into adipocytes and chondrocytes.…”

Effects of Long-Term Hypoxia and Pro-Survival Cocktail in Bone Marrow-Derived Stromal Cell Survival

“…It has also been suggested that BMSC stemness under various conditions may be defined as the ability to differentiate in vivo and support hematopoietic elements [37]. Superparamagnetic iron oxide nanoparticle labeling of BMSCs does not affect their stemness [38]. In the current study, it was evident that BMSCs had a significantly greater proliferation rate when grown in low oxygen tension compared with normoxia after an initial lag phase.…”

Translational Imaging for Regenerative Medicine

“…Superparamagnetic iron oxide nanoparticles (SPIONs) are U.S. Food and Drug Administration-approved MRI contrast agents and are already used in clinics; thus they are reasonable candidates for in vivo imaging in tissue engineering and regenerative medicine. Various cells, for example, adipocytes, mesenchymal stem cells, neural stem cells (NSCs), human adipose-derived stromal cells, chondrocytes, and smooth muscle cells, can be easily labeled with SPIONs [55][56][57][58][59]. In addition to cells, SPIONs can be incorporated into engineered scaffolds before implantation, and their location and degradation can be monitored using MRI [17].…”