Tracking Transplanted Stem Cell Migration Using Bifunctional, Contrast Agent-Enhanced, Magnetic Resonance Imaging

Modo, Mike; Cash, Diana; Mellodew, Karen; Williams, Steven; Fraser, Scott E.; Meade, Thomas J.; Price, Jack; Hodges, Helen

doi:10.1006/nimg.2002.1194

Cited by 248 publications

(139 citation statements)

References 15 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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“…Alternative attempts of MR contrast agents designed to combine the advantages of fluorescence and magnetic resonance imaging techniques have been described before (8,12,13). These comprised the lanthanide chelators DTPA and DOTA, which were bound to Gadolinium and covalently attached to fluorescent dyes (8, 13) and arginyl peptides, which were cross-linked to magnetic nanoparticles and attached to the indocyanine dye Cy 5.5 (12).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, cell labeling procedures might aid to identify and trace the fate of the transplanted cells. To allow a depiction of transplanted cells in vivo with imaging modalities, several methods have been designed to label stem cells with fluorescent dyes or contrast agents prior to administration (5)(6)(7)(8)(9)(10)(11). However, the optimal imaging technique to be used for an in vivo tracking of the transplanted cells is still under debate.…”

Section: Introductionmentioning

confidence: 99%

“…Bifunctional contrast agents, which could be detected at the same time by magnetic resonance (MR) imaging, optical imaging (OI) and fluorescence microscopy, would allow to integrate advantages of conceptually highly different imaging techniques (8,12,13): high three-dimensional anatomical resolution provided in-vivo by MR, high sensitivity provided by OI and detection at a cellular level provided by fluorescence microscopy, respectively. Furthermore, limitations of each technique, such as low sensitivity of MR, little anatomic background information obtained with OI and ex vivo information obtained with fluorescence microscopy, could be compensated by the other techniques.…”

Section: Introductionmentioning

confidence: 99%

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Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy

Daldrup-Link

Rudelius

Metz

et al. 2004

Eur J Nucl Med Mol Imaging

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Purpose: To assess the feasibility of Gadophrin-2 to trace intravenously injected human hematopoietic cells in athymic mice using magnetic resonance (MR) imaging, optical imaging (OI) and fluorescence microscopy. Materials and Methods: Mononuclear peripheral blood cells from GCSF-primed patients were labeled with Gadophrin-2 (Schering AG, Berlin, Germany), a paramagnetic and fluorescent metalloporphyrin, using established transfection techniques with cationic liposomes. The labeled cells were evaluated in vitro with electron microscopy and ICP-AES. Then, 1×106 -3×10 8 labeled cells were injected into 14 nude Balb/c mice and the in vivo cell distribution was evaluated with MR and OI before as well as 4, 24 and 48 hours (h) after intravenous injection (p.i.=post injection). Five additional mice served as controls: three mice were non-treated controls and two mice were investigated after injection of nonlabeled cells. The contrast agent effect was determined quantitatively for MR by calculating ΔSI(%)-data. After completion of in vivo imaging studies, fluorescence microscopy of excised organs was performed.

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“…35,36 Similar dual optical/MRI contrast has been described using visible-wavelength fluorophores and Gd 3ϩ chelators conjugated to high-molecular-weight scaffolds such as dextran. 26 Large nanoparticles generating simultaneous MRI, ultrasound, and fluorescence contrast have also been described (reviewed in Wickline and Lanza 37 ) and might prove useful for multimodality stem cell tracking.…”

Section: Multimodality Contrast Agentsmentioning

confidence: 99%

In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease

2004

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Abstract-Various stem cells hold promise for the treatment of human cardiovascular disease. Regardless of stem cell origin, future clinical trials will require that the location and number of such cells be tracked in vivo, over long periods of time. The problem of tracking small numbers of cells in the body is a difficult one, and an optimal solution does not yet exist. We review the many contrast agents and detectors that have been proposed for stem cell tracking during clinical trials, define the characteristics of an ideal imaging technology, and suggest future directions for research. For example, stem cell therapy for heart failure addresses an important problem in clinical medicine. Heart failure is a major cause of morbidity and mortality in the United States. The rates of new and recurrent heart failure events increase substantially with age. In patients aged 65 and older, congestive heart failure is the single most frequent cause of hospitalization in the United States. Despite substantial advances in the clinical management of heart failure, the diagnosis continues to carry a grave prognosis with an overall 5-year mortality rate of Ϸ50%. This rate is substantially worse in more severely affected patient subsets. An understanding of the role of stem cells in repopulating damaged areas in the heart would help target these diseased areas. 1 The problem of imaging small numbers of cells in the living subject is not limited to stem cell-based treatments in cardiology but has broad applicability in oncology, immunology, and transplantation. Ideal Imaging Technology for Stem Cell TrackingSuccessful in vivo imaging requires that a contrast agent associated with a stem cell exert an "effect size" sufficient for detection by imaging hardware. Although the most attractive contrast agents for tracking are endogenous ones (ie, normal components of the stem cell), their effect size is extremely small. This review will focus on exogenous contrast agents, which have a large and controllable effect size. It also will focus on imaging technology that has clinical relevance because many preclinical small animal studies in the field of stem cell tracking are not translatable to clinical practice. The 8 characteristics of an ideal imaging technology for stem cell tracking are presented in Table 1. First, and foremost, the exogenous contrast agent must be biocompatible, safe, and nontoxic. This is especially important when nanotechnology solutions to the tracking problem (mentioned below) are considered, because most solid-state devices will be composed of materials that do not have proven long-term safety in vivo.Another consideration is the need for genetic modification of the stem cell or perturbation of its genetic program by the contrast agent itself. Several imaging techniques, such as enzymatic conversion of an injected substrate and receptorbased binding, require stable integration of transgenes. This strategy may be combined with genetic manipulation of stem cell populations to enhance the viability, differentiatio...

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Tracking Transplanted Stem Cell Migration Using Bifunctional, Contrast Agent-Enhanced, Magnetic Resonance Imaging

Cited by 248 publications

References 15 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

Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy

In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease

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