MR Tracking of Magnetically Labeled Mesenchymal Stem Cells in Rat Kidneys with Acute Renal Failure

Abstract

Stem cell transplantation is emerging as a potential treatment option for acute renal failure (ARF) because of its capability to regenerate tissues and organs. To better understand the mechanism of cell therapy, in vivo tracking cellular dynamics of the transplanted stem cells is needed. In the present study, in vivo monitored magnetically labeled mesenchymal stem cells (MSCs) were transplanted intravascularly into an ARF rat model using a conventional magnetic resonance imaging (MRI) system. Rat bone marrow MSCs were labeled with home synthesized Fe 2 O 3 -PLL, and labeled (n = 6) or unlabeled MSCs (n = 6) were injected into the renal arteries of the rats with ARF induced by the intramuscular injection of glycerol. Using the same technique, labeled MSCs were also injected into the rats assigned to a control group (n = 8). MR images of kidneys were obtained before injection of MSCs as well as immediately, 1, 3, 5, and 8 days afterwards. MR findings were analyzed and compared with histopathological and immunohistochemical results. These results showed that the rat MSCs were successfully labeled with the home synthesized Fe 2 O 3 -PLL. In both renal failure and intact rat models, the labeled MSCs demonstrated a loss of signal intensity in the renal cortex on T2*-weighted MR images, which was visible up to 8 days after transplantation. Histological analyses showed that most of the labeled MSCs that tested positive for Prussian blue staining were in glomerular capillaries, corresponding to the areas where a loss in signal intensity was observed in the MRI. A similar signal intensity decrease was not detected in the rats with unlabeled cells. These data demonstrate that the magnetically labeled MSCs in the rat model of ARF were successfully evaluated in vivo by a 1.5 T MRI system, showing that the mechanisms of stem cell therapy have great potential for future ARF treatment recipients.

In Vivo Tracking of Dual‐Labeled Mesenchymal Stem Cells Homing Into the Injured Common Carotid Artery

“…Recently, a number of reports described labeling and tracking of cells through the use of SPIO nanoparticles or fluorescent dyes (Soriano et al, 1992;Hill et al, 2003;Kraitchman et al, 2003;Werner et al, 2003;Bos et al, 2004;Kong et al, 2004a,b;Corti et al, 2005;Sun et al, 2005Sun et al, , 2008Ju et al, 2007). Moreover, the small animal in vivo imaging systems permit sensitive and quantitative spatial monitoring of markers in whole animals.…”

“…Synthesized 8 g/L ferric oxide nanoparticles coupling with poly-L-lysine (Fe 2 O 3 -PLL), with core particle size of 15 AE 5 nm and saturation magnetization of 60A*M2/kg, was added to Passage 3 (P3) BMSC cell culture medium to a final concentration of 20 lg/mL for labeling (Ju et al, 2007;Sun et al, 2008). Cells were labeled at 37 C, 5% CO 2 incubator for 24 hr, and washed repeatedly with phosphate buffer.…”

“…In our previous studies, we have successfully performed 1.5T MR imaging of magnetic labeled cells (Ju et al, 2007;Sun et al, 2008). More recently, 7T micromagnetic resonance imaging (7T micro-MR) specifically designed for small animals was established in our laboratory, enabling the imaging with high contrast and excellent spatiotemporal resolution up to micrometers.…”

Efficient and Rapid Labeling of Transplanted Cell Populations with Superparamagnetic Iron Oxide Nanoparticles Using Cell Surface Chemical Biotinylation for in Vivo Monitoring by MRI

“…translocating peptides (20,33). Alternatively, cells have been tracked in vivo by surface labeling of cells using Magnetic resonance imaging (MRI) is a commonly employed noninvasive imaging modality and cells have cell-specific antibodies that are also conjugated to contrast agents (1 Chemical biotinylation of cells involve reaction of line) were cultured in Dulbecco's modified Eagle's medium (DMEM, Sigma-Aldrich Co. Ltd., Poole, UK) supthe N-hydroxysuccinimide (NHS) ester group of biotinylation reagents to the -amine of lysine residues or the plemented with 10% heat-inactivated fetal calf serum (FCS, Invitrogen, Paisley, UK) at 37°C at 5% CO 2 .…”

“…Labeling of cells for MRI monitoring usually involves and also for the development of cell-based therapies (11,28,36,42). Until relatively recently, tracking particuinternalization of contrast agents, with or without assistance from, for example, polycationic compounds or lar cell populations in vivo has not been possible, such information being derived only from ex vivo histology.translocating peptides (20,33). Alternatively, cells have been tracked in vivo by surface labeling of cells using Magnetic resonance imaging (MRI) is a commonly employed noninvasive imaging modality and cells have cell-specific antibodies that are also conjugated to contrast agents (1 Chemical biotinylation of cells involve reaction of line) were cultured in Dulbecco's modified Eagle's medium (DMEM, Sigma-Aldrich Co. Ltd., Poole, UK) supthe N-hydroxysuccinimide (NHS) ester group of biotinylation reagents to the -amine of lysine residues or the plemented with 10% heat-inactivated fetal calf serum (FCS, Invitrogen, Paisley, UK) at 37°C at 5% CO 2 .…”