Magnetic Resonance Imaging with Superparamagnetic Iron Oxide Fails to Track the Long-term Fate of Mesenchymal Stem Cells Transplanted into Heart

Abstract

MRI for in vivo stem cell tracking remains controversial. Here we tested the hypothesis that MRI can track the long-term fate of the superparamagnetic iron oxide (SPIO) nanoparticles labelled mesenchymal stem cells (MSCs) following intramyocardially injection in AMI rats. MSCs (1 × 106) from male rats doubly labeled with SPIO and DAPI were injected 2 weeks after myocardial infarction. The control group received cell-free media injection. In vivo serial MRI was performed at 24 hours before cell delivery (baseline), 3 days, 1, 2, and 4 weeks after cell delivery, respectively. Serial follow-up MRI demonstrated large persistent intramyocardial signal-voids representing SPIO during the follow-up of 4 weeks, and MSCs did not moderate the left ventricular dysfunction. The TUNEL analysis confirmed that MSCs engrafted underwent apoptosis. The histopathological studies revealed that the site of cell injection was infiltrated by inflammatory cells progressively and the iron-positive cells were macrophages identified by CD68 staining, but very few or no DAPI-positive stem cells at 4 weeks after cells transplantation. The presence of engrafted cells was confirmed by real-time PCR, which showed that the amount of Y-chromosome-specific SRY gene was consistent with the results. MRI may not reliably track the long-term fate of SPIO-labeled MSCs engraftment in heart.

The long-term fate of mesenchymal stem cells labeled with magnetic resonance imaging-visible polymersomes in cerebral ischemia

“…This finding has not been reported in previous studies on myocardial infarction. 13,14,16 As histology revealed a remarkable cell apoptosis at 1 week after transplantation, the apoptosis of grafted cells might mainly contribute to the drop of such low signal volume. Our results also showed that a small fraction of MSCs can survive for a long period of 8 weeks after transplantation.…”

“…9,13,16,17 It has been reported that SPIONbased MRI cannot provide reliable information on long-term viability and might overestimate the survival of SPIONlabeled stem cells in myocardial infarction. 13,14 In our study, the dynamic change of low signal volume on MRI was consistent with the change pattern of the number of viable cells.…”

“…13,14 The ability of SPION-based MRI to reliably evaluate long-term cell engraftment and survival remains controversial. Further studies have shown that long-lasting hypo-signal intensity on MRI mainly originated from macrophages that engulfed SPION, 15,16 or from extracellular iron particles that persisted in the interstitial space after the grafted labeled cells died. 17 However, almost all of these investigations mainly focused on cell fate in myocardial infarction.…”

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

“…[11][12][13][14][15] For these reasons, monitoring of cell therapies is of high clinical relevance and, despite several challenges to overcome, magnetic resonance imaging (MRI) continues to be the method of choice, offering high tissue penetration depth and spatial resolution in comparison with alternative methods. 16,17 Drawbacks of MRI such as low specificity due to unspecific signal from phagocytosed injected cells, dead cells, or local hemorrhage 14,18,19 have been shown to limit the use of MRI for cell imaging in longitudinal studies, and considerable research efforts are devoted to finding alternative/complementary methods. 19,20 With their strong negative contrast in T2-or T2*-weighted MR images, superparamagnetic iron oxide nanoparticles (NPs) are the most common contrast agents used to label cells for MRI cell tracking.…”

“…16,17 Drawbacks of MRI such as low specificity due to unspecific signal from phagocytosed injected cells, dead cells, or local hemorrhage 14,18,19 have been shown to limit the use of MRI for cell imaging in longitudinal studies, and considerable research efforts are devoted to finding alternative/complementary methods. 19,20 With their strong negative contrast in T2-or T2*-weighted MR images, superparamagnetic iron oxide nanoparticles (NPs) are the most common contrast agents used to label cells for MRI cell tracking. The two most widely used NPs were initially developed and approved by the US Food and Drug Administration (FDA) for liver imaging.…”