Nanocrystals with advanced magnetic or optical properties have been actively pursued for potential biological applications, including integrated imaging, diagnosis and therapy. Among various magnetic nanocrystals, FeCo has superior magnetic properties, but it has yet to be explored owing to the problems of easy oxidation and potential toxicity. Previously, FeCo nanocrystals with multilayered graphitic carbon, pyrolytic carbon or inert metals have been obtained, but not in the single-shelled, discrete, chemically functionalized and water-soluble forms desired for biological applications. Here, we present a scalable chemical vapour deposition method to synthesize FeCo/single-graphitic-shell nanocrystals that are soluble and stable in water solutions. We explore the multiple functionalities of these core-shell materials by characterizing the magnetic properties of the FeCo core and near-infrared optical absorbance of the single-layered graphitic shell. The nanocrystals exhibit ultra-high saturation magnetization, r1 and r2 relaxivities and high optical absorbance in the near-infrared region. Mesenchymal stem cells are able to internalize these nanoparticles, showing high negative-contrast enhancement in magnetic-resonance imaging (MRI). Preliminary in vivo experiments achieve long-lasting positive-contrast enhancement for vascular MRI in rabbits. These results point to the potential of using these nanocrystals for integrated diagnosis and therapeutic (photothermal-ablation) applications.
In particular, hESCECs showed significant bioluminescence signals at day 2, which decreased progressively over the following 4 weeks, whereas bioluminescence signals from undifferentiated hES cells increased dramatically during the same period. Postmortem histology and immunohistochemistry confirmed teratoma formation after injection of undifferentiated hES cells but not hESC-ECs. From these data taken together, we concluded that reporter gene is a better marker for monitoring cell viability, whereas iron particle labeling is a better marker for high-resolution detection of cell location by MR. Furthermore, transplantation of predifferentiated rather than undifferentiated hES cells would be more suited for avoiding teratoma formation. STEM CELLS 2008;26:864 -873 Disclosure of potential conflicts of interest is found at the end of this article.
Macrophages play important roles in the immunological defense system, but at the same time they are involved in inflammatory diseases such as atherosclerosis. Therefore, imaging macrophages is critical to assessing the status of these diseases. Toward this goal, a recombinant human H chain ferritin (rHFn)-iron oxide nano composite has been investigated as an MRI contrast agent for labeling macrophages. Iron oxide nanoparticles in the form of magnetite (or maghemite) with narrow size distribution were synthesized in the interior cavity of rHFn. The composite material exhibited the R 2 relaxivity comparable to known iron oxide MRI contrast agents. Furthermore, the mineralized protein cages are readily taken up by macrophages in vitro and provide significant T2* signal loss of the labeled cells. These results encourage further investigation into the development of the rHFn-iron oxide contrast agent to assess inflammatory disease status such as macrophage-rich atherosclerotic plaques in vivo. Magn Reson Med 60:1073-1081, 2008.
To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions.
This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.
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