DOI: 10.1148/radiol.2473071876
(Radiology 2008;247:913-914.)
© RSNA, 2008
Transferrin Receptor Expression in Iron Oxide–labeled Mesenchymal Stem Cells
Edyta Pawelczyk, PhD and
Joseph A. Frank, MS, MD
Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892
e-mail: pawelczyke{at}cc.nih.gov
Editor:
In the August 2007 issue of Radiology, Dr Schäfer and colleagues (1) reported the upregulation of transferrin receptor (CD71) on rat mesenchymal stem cells (MSCs) labeled with superparamagnetic iron oxide (SPIO) nanoparticles. The authors should be commended for studying changes in the iron metabolism or storage to ensure safety of SPIO cell labeling. However, their results and conclusions cannot be generalized to all SPIO nanoparticles and transfection agents (TAs) used for cell labeling.
The authors report the upregulation of CD71 on late-passage (ie, passages 7–16) rat MSCs after labeling with ferucarbotran. Multiple passages of human and mouse MSCs are prone to genetic instability with consequent malignant transformation (2,3). Later passage (ie, passages >5) is not biologically relevant since human MSCs become senescent after 20–40 population doublings in culture (4). Human MSCs are positive for the transferrin receptor (5,6), however the authors showed no CD71 expression in control rat MSCs (see figure 3 of their article). Therefore, the upregulation of transferrin receptor in the ferucarbotran-labeled rat MSCs is not clinically relevant. Ferumoxides–protamine sulfate labeled human MSCs have an expected transient decrease in CD71 messenger RNA and protein levels when compared to unlabeled cells (6).
The authors avoided comparing their findings to magnetic labeling of MSCs with ferumoxides and TAs such as poly-l-lysine or protamine sulfate (7–12). The authors report that the ferucarbotrans complexed to DOSPER or jetPEI (1) coated the cell surface but were not internalized. Ferumoxides complexed to poly-l-lysine (12) or protamine sulfate (8,9) are located in endosomes in human MSCs and other cells. Protamine sulfate facilitates the endosomal incorporation of ferumoxides in human MSCs and does not alter the differentiation capacity or viability of stem cells (8,10). The authors suggest that labeling MSCs with SPIO nanoparticles may affect homing capability of the stem cells. We have shown that ferumoxides-TA labeled human MSCs will home to liver (7), tumors (11), or heart (13), demonstrated at magnetic resonance imaging and confirmed at histologic evaluation. The author's concern about the alteration in cell homing is not warranted, especially when the SPIO-TA complexes are localized in endosomes. Although the authors describe the study's limitations, they overstate the clinical relevance and potential translation of their results. The authors' Advances in Knowledge statement that SPIO-TA or ultrasmall SPIO–TA complexes only coat the MSCs is not applicable to ferumoxides-TA complexes and human MSCs. The concerns raised by the authors are only pertinent to this study and are inaccurate when ferumoxides are complexed to protamine sulfate and human MSCs.
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References
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