Abstract
Background aims
Tracking the fate of cells after infusion would be a valuable asset for many stem
cell therapies, but very few (cell) labels are approved for human therapeutic use.
Superparamagnetic iron oxide particles (SPIO) can be internalized into stem cells
in vitro to allow real-time tracking with gradient echo magnetic resonance imaging, but SPIO
are approved for (diagnostic) imaging and not for (therapeutic) cell labeling in vivo. In this study, we investigated the possibility of labeling stem cells with an SPIO
approved for patient use, albeit in a novel manner by enhancing uptake with the use
of a transfection agent, also approved for patient use. Although there are many reports
of hematopoietic stem cells being labeled with SPIO, there is some controversy regarding
the efficiency of this and whether undifferentiated CD34+ progenitor (stem) cells
are able to take up iron in the absence of a transfection agent to enhance the process.
Methods
Human CD34+ cells were treated in vitro as follows: incubation with (i) medium only (control), (ii) ferumoxide (Endorem)
and (iii) ferumoxide (Endorem) plus exposure to a transfection agent (protamine sulfate).
Cells were incubated for 2, 4 and 24 hours and assessed for viability, differentiation
capacity and visualized in vitro with 3-T magnetic resonance imaging. The cells were also analyzed by means of flow
cytometry and morphology examined by electron microscopy.
Results
CD34+ hematopoietic progenitor cells can internalize ferumoxide (Endorem) independently
of a transfection agent. However, uptake of ferumoxide is enhanced after exposure
to protamine sulfate. Iron labeling of CD34+ cells in this manner does not affect
cell viability and does not appear to affect the potential of the cells to grow in
culture. Iron-labeled CD34+ cells can be visualized in vitro on 3-T magnetic resonance image scanning.
Conclusions
Endorem and protamine sulfate can be combined to promote iron oxide nanoparticle uptake
by CD34+ cells, and this methodology can potentially be used to track the fate of
cells in a clinical trial setting because both compounds are (separately) approved
for clinical use.
Key Words
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Article info
Publication history
Accepted:
October 23,
2012
Received:
June 8,
2012
Identification
Copyright
© 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
