In vivo tracking of bone marrow stromal cells transplanted into mice cerebral infarct by fluorescence optical imaging

Shichinohe, Hideo; Kuroda, Satoshi; Lee, Jang Bo; Nishimura, Goro; Yano, Shunsuke; Seki, Takahiro; Ikeda, Jun; Tamura, Mamoru; Iwasaki, Yoshinobu

doi:10.1016/j.brainresprot.2004.04.004

Cited by 80 publications

(49 citation statements)

References 26 publications

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“…In recent years, to monitor the transplanted MSCs, several non-invasive in vivo molecular imaging tracking techniques have been developed, including nuclear medicine, optical imaging and MRI (14)(15)(16). The MR technique holds promising advantages due to its wide imaging window, high temporal and spatial resolution, and good contrast, without ionic radiation.…”

Section: Discussionmentioning

confidence: 99%

Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro

et al. 2011

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Abstract. Mesenchymal stem cell (MSC) transplantation provides a novel strategy for the treatment of human disease. MR imaging (MRI) is able to track transplanted stem cells labeled with superparamagnetic iron oxide (SPIO) in vivo. However, the effect of SPIO upon labeled MSCs remains unclear on a cellular level. In this study, the biological characteristics of rat MSCs labeled with home-synthesized SPIO particles were evaluated. The MSCs were isolated from the bone marrow of 5 adult Sprague-Dawley rats and labeled with home-synthesized SPIO particles at a final iron concentration of 20 µg/ml. Labeled MSCs were confirmed with Prussian blue staining and transmission electron microscopy. The quantity of iron per cell was determined by atomic absorption spectrometry. Cell viability, proliferation, membranous antigen and multiple differentiation ability were compared between labeled and unlabeled MSCs. The rat MSCs were effectively labeled and the labeling efficiency was approximately 100%, as revealed by Prussian blue staining. The SPIO particles located in the endosomal vesicles of the MSCs were confirmed by transmission electron microscopy. No significant differences were observed in cell viability, proliferation, membranous antigen and multiple differentiation ability between the labeled and unlabeled MSCs (P>0.05). In conclusion, MSCs are able to be effectively labeled by home-synthesized SPIO particles without influencing their main biological characteristics. IntroductionAs a potential interventional procedure, stem cell transplantation provides a new strategy for the treatment of incurable human diseases and organ failure (1-3). The plasticity of bone marrow mesenchymal stem cells (MSCs) has been intensively investigated, since this approach generates less ethical and social controversies. The use of bone marrow MSCs also offers several advantages, including ease of collection and rapid in vivo and in vitro repopulation. Numerous studies have shown that MSCs are capable of forming functional components of organ tissues, including the kidney, heart and liver (1-4).A non-invasive in vivo technique that permits evaluation of the efficiency of transplantation and the potential migration of transplanted cells would prove to be an essential tool for treatment assessment. To better understand the mechanisms of the cell therapy, in vivo monitoring of the cellular dynamics of the transplanted MSCs has been proposed. Recently, MR imaging (MRI) has proven to be effective in tracking the distribution of transplanted MSCs in vivo by way of labeling cells with superparamagnetic iron oxide (SPIO) particles (5-7).However, it is not clear whether the SPIO labeling technique of MSCs is safe. Additionally, the effect of SPIO upon labeled cells remains unclear on a cellular level (8). Thus, the purpose of the present study was to investigate whether and how the labeling of MSCs with SPIO affects the biological characteristics of MSCs. Materials and methodsCell culture. This study was approved by our institutional Animal Use and...

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Section: Discussionmentioning

confidence: 99%

Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro

et al. 2011

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“…Among the MR MSCs is a valuable tool in determining the mechanisms of how MSCs restore renal structures, ameliorate renal tracing agents, SPIO appears to be gaining popularity (5) because SPIO particles in nanometeric size have function, and improve cell metabolism. Great progress has recently been made in cellular tracking technique strong penetrating capability, which makes it possible to cause signal change in MRI at a super-low tracer conusing nuclear medicine imaging (10), optical imaging (18), and MRI. Among these noninvasive in vivo trackcentration (nanomolar level).…”

Section: Characterization Of Mscsmentioning

confidence: 99%

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

Sun

Teng

et al. 2008

Cell Transplant

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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.

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“…Data are mean ± SEM. *, P ＜ 0.05. con, control; PI, preinduction. into neuron in vitro (Sanchez-Ramos et al, 2000;Woodbury et al, 2002) as well as in vivo (Shichinohe et al, 2004), although it is still controversial if BMSCs indeed transdifferentiate into neuronal cells (Cogle et al, 2004;Munoz-Elias et al, 2004), or transplanted BMSCs fuse to resident cells expressing BMSC-derived markers (AlvarezDolado et al, 2003;Weimann et al, 2003). To support the clinical potential of BMSC transplantation, many attempts to differentiate BMSCs in vitro into neural cells have been made.…”

Section: Introductionmentioning

confidence: 99%

Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells

Cho

Jang

et al. 2009

Exp Mol Med

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When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2α phosphorylation. Transcription of two downstream targets of eIF2α, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuro-

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In vivo tracking of bone marrow stromal cells transplanted into mice cerebral infarct by fluorescence optical imaging

Cited by 80 publications

References 26 publications

Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro

Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro

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

Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells

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