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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

SPIO

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

BMSCs

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