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Table 2 Intrahepatic animal stem cell tracking studies with MRI

From: Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration

Study Species (n) Animal model Cell type Agent Delivery/number of cells infused Study observations
Pang et al., 2015 [22] Rats (18) CCl4-induced liver fibrosis model Allogeneic BMSCs PEG-g-PEI-SPIO Mesenteric vein/106 Detection of modified cells for up to 2 weeks post transplantation
Labeled cells were still present in the liver intralobular parenchyma after 2 weeks
The labeling process displayed good biocompatibility
Zhao et al., 2014 [23] Mice (12) CCl4-induced liver injury model Xenogeneic AD-MSCs SPIO Splenic vein/107 Hypointense MRI images were detected until 7 days
The attenuation of MRI signals mainly arose from excretion of SPIO
Fluorescence and PB staining showed that the SPIO particles were still inside the stem cells
The location of AD-MSC accumulation was well integrated with the liver injury focus
Chen et al., 2012 [25] Rats (40) PHx-induced liver injury model Allogeneic BMSCs SPIO Directly intrahepatic into residual lobe/106 An oval hypointense area at injection sites was visible within 2 weeks by MRI, while the signal intensity decreased with time
PB stain showed the presence of Feridex-labeled cells in the liver sinusoid
Wang et al., 2014 [26] Mice (12) CCl4-induced liver injury model Allogeneic EPCs SPIO Caudal vein/106 Detection of grafted cells after 8 days
PB stain revealed SPION containing stem cells accumulated in the liver parenchyma, particularly along sinusoids and portal areas
Bos et al., 2004 [27] Rats (4) CCl4-induced ALF model Allogeneic BMSCs SPIO Portal vein/106 Detection of cells up to 12 days
Signal intensity loss of MRI appeared a granular pattern
Matching areas stained positive for PB and CD90 antigen of postmortem liver tissue showed the SPIO particles were retained in the originally labeled cells
Cai et al., 2008 [28] Rats (30) CCl4-induced ALF model Allogeneic BMSCs SPIO Hepatic artery/106 Hypointense MRI images faded over time and were detected within 7 days
Cell viability was not impaired by labeling procedure for up to 4 weeks
PB staining and DAPI-stained blue fluorescent nuclei showed the presence of original iron particles containing cells
Zhou et al., 2010 [29] Rats (18) CCl4-induced liver fibrosis model Allogeneic BMSCs SPIO Mesenteric vein/106 Detection of grafted cells for 12 days in BMSC-labeled group, but for only 3 days in cell-free SPIO group
PB staining showed the presence of originally labeled cells in the portal region at 3 days, and mainly in the injured areas of intralobular parenchyma at 15 days
Kim et al., 2010 [31] Rats (14) DMN-induced liver fibrosis model Xenogeneic BMSCs MNP
Intrasplenic injection/106 Detection of transplanted cells after 14 days
The decrease of MRI signal intensity was more obvious in MNP-tagged group. Masson trichrome staining and autofluorescent images of MNP-tagged cells showed most stem cells migrated to the fibrous septa
Ju et al., 2007 [32] Rats (12) CCl4-induced liver cirrhosis model Allogeneic
SPIO Splenic vein/106 Detection of injected cells for up to 2 weeks
No visible blue particles were found in unlabeled cells after PB staining
Grafted cells were mainly distributed in periportal and injured areas
  1. CCl4 carbon tetrachloride, BMSC bone marrow-derived mesenchymal stem cell, PEG-g-PEI-SPIO superparamagnetic iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine, AD-MSC adipose-derived mesenchymal cell, SPIO superparamagnetic iron oxides, PB Prussian blue, DAPI 4′,6-diamidino-2-phenylindole, PHx partial hepatectomy; MRI magnetic resonance imaging; EPC endothelial progenitor cell, ALF acute liver failure; DMN dimethylnitrosamine; MNP fluorescent magnetic nanoparticle