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. 2016 Jul 29;65(3):311-8.
doi: 10.1538/expanim.15-0125. Epub 2016 Apr 11.

Tracking cells implanted into cynomolgus monkeys (Macaca fascicularis) using MRI

Yasuyo Ito-Fujishiro  1 , Hiroshi Koie, Hiroaki Shibata, Sachi Okabayashi, Yuko Katakai, Chieko Ohno, Kiichi Kanayama, Yasuhiro Yasutomi, Naohide Ageyama
Affiliations

Tracking cells implanted into cynomolgus monkeys (Macaca fascicularis) using MRI

Yasuyo Ito-Fujishiro et al. Exp Anim. .

Abstract

Regenerative therapy with stem cell transplantation is used to treat various diseases such as coronary syndrome and Buerger's disease. For instance, stem-cell transplantation into the infarcted myocardium is an innovative and promising strategy for treating heart failure due to ischemic heart disease. Basic studies using small animals have shown that transplanted cells improve blood flow in the infarcted region. Magnetic resonance imaging (MRI) can noninvasively identify and track transplanted cells labeled with superparamagnetic iron oxide (SPIO). Although clinical regenerative therapies have been clinically applied to patients, the fate of implanted cells remains unknown. In addition, follow-up studies have shown that some adverse events can occur after recovery. Therefore, the present study evaluated the ability of MRI using a 3T scanner to track implanted peripheral blood mononuclear cells labeled with SPIO on days 0 and 7 after intramuscular (i.m.) and intravenous (i.v.) injection into a cynomolgus monkey. Labeled cells were visualized at the liver and triceps surae muscle on MR images using T1- and T2-weighted sequences and histologically localized by Prussian blue staining. The transplanted cells were tracked without abnormal clinical manifestations throughout this study. Hence, MRI of cynomolgus monkey transplanted SPIO-labeled cells is a safe and efficient method of tracking labeled cells that could help to determine the mechanisms involved in regenerative therapy.

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Figures

Fig. 1.
Fig. 1.
Peripheral blood mononuclear cells labeled with SPIO and visualized by microscopy. Feridex (A) and Resovist (B) labeling (magnification, × 1,000). Blue spots in pink regions indicate magnetically-labeled nuclei stained with Prussian blue. Feridex particles are larger than Resovist particles. SPIO, superparamagnetic iron oxide.
Fig. 2.
Fig. 2.
T1-weighted MR images of the long axis (A and B) and transverse (C and D) of the triceps surae muscle. Days 0 (A and C) and 7 (B and D) after transplantation. Black spots with white arrows indicate magnetic labeling as negative contrast. MR, magnetic resonance.
Fig. 3.
Fig. 3.
T2-weighted MR images of the long axis of the triceps surae muscle. Days 0 (A) and 7 (B) after transplantation. Black spots with white arrows indicate magnetic labeling as negative contrast. MR, magnetic resonance.
Fig. 4.
Fig. 4.
T1- and T2-weighted MR images of the short axis of the liver shortly after injection into the saphenous vein on day 0 (A and B, respectively) and images of non-labeled injected cells (C and D, respectively). White arrows show SPIO signals. MR, magnetic resonance.
Fig. 5.
Fig. 5.
Remains of SPIO in macrophages at the triceps surae muscle (magnification, × 400). Blue spots indicate residues of labeled cells after injection i.m. SPIO, superparamagnetic iron oxide.
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