1H-NMR (
nuclear magnetic resonance) imaging is regularly proposed to non-invasively monitor
cell therapy protocols.
Prior to transplantation, cells must be loaded with an
NMR contrast agent (CA). Most studies performed so far make use of superparamagnetic
iron oxide particles (SPIOs), mainly for favorable detection sensitivity. However, in the case of labeled
cell death, SPIO recapture by
inflammatory cells might introduce severe bias. We investigated whether
NMR signal changes induced by preloading with SPIOs or the low molecular weight
gadolinium (Gd)-
DTPA accurately monitored the outcome of transplanted cells in a murine model of acute immunologic rejection. CA-loaded human
myoblasts were grafted in the
tibialis anterior of
C57BL/6 mice.
NMR imaging was repeated regularly until 3 months post-transplantation. Label outcome was evaluated by the size of the labeled area and its relative contrast to surrounding tissue. In parallel,
immunohistochemistry assessed the presence of
human cells.
Data analysis revealed that CA-induced signal changes did not strictly reflect the
graft status. Gd-DTPA label disappeared rapidly yet with a 2-week delay compared with
immunohistochemical evaluation. More problematically, SPIO label was still visible after 3 months, grossly overestimating cell survival (<1 week). SPIOs should be used with extreme caution to evaluate the presence of grafted cells in vivo and could hardly be recommended for the long-term monitoring of cell transplantation protocols.
