Optical imaging of progenitor cell homing to patient-derived tumors
University of California, San Diego, CA, 92103-8756, USA. .Contrast Media & Molecular Imaging (Impact Factor: 2.92). 11/2012; 7(6):525-36. DOI: 10.1002/cmmi.1485
Capitalizing on cellular homing to cancer is a promising strategy for targeting malignant cells for diagnostic, monitoring and therapeutic purposes. Murine C17.2 neural progenitor cells (NPC) demonstrate a tropism for cell line-derived tumors, but their affinity for patient-derived tumors is unknown. We tested the hypothesis that NPC accumulate in patient-derived tumors at levels detectable by optical imaging. Mice bearing solid tumors after transplantation with patient-derived leukemia cells and untransplanted controls received 10(6) fluorescent DiR-labeled NPC daily for 1-4 days, were imaged, then sacrificed. Tissues were analyzed by immunofluorescence and flow cytometry to detect tumor cell engraftment (CD45) and NPC (FITC-β galactosidase or DiR). Tumors consisted primarily of CD45-positive cells and demonstrated mild fluorescence, corresponding to frequent clusters of FITC-β gal-positive cells. Both transplanted and control mice demonstrated the highest fluorescent signal in the spleens and other tissues of the reticuloendothelial activating system. However, only rare FITC-β gal-positive cells were detected in the mildly engrafted transplanted spleens and none in the control spleens, suggesting that their high DiR signal reflects the sequestration of DiR-positive debris. The mildly engrafted transplanted kidneys demonstrated low fluorescent signal and rare FITC-β gal-positive cells whereas control kidneys were negative. Results indicate that NPC accumulate in tissues containing patient-derived tumor cells in a manner that is detectable by ex vivo optical imaging and proportional to the level of tumor engraftment, suggesting a capacity to home to micrometastatic disease. As such, NPC could have significant clinical applications for the targeted diagnosis and treatment of cancer. Copyright © 2012 John Wiley & Sons, Ltd.
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ABSTRACT: Liver cell transplantation was developed as a therapeutic alternative to solid liver transplantation in the management of liver-based metabolic disorders and may be useful for the treatment of acute or chronic liver failure. While clinical studies have demonstrated temporal amelioration of the symptoms of metabolic liver disorders by transplanted liver cells, the long-term outcome of liver cell transplantation is still insufficient. A major limitation for improving liver cell transplantation is the inability to track the fate of cells once they have been infused. Radionuclide-based imaging, MRI and optical methods have been investigated as methods for noninvasive monitoring of liver cell transplantation. This article summarizes and critically discusses these approaches, with a special focus on MRI-based tracking of transplanted liver cells and provides an outlook on possible clinical applications for the near future.
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ABSTRACT: A multifunctional system, combining two modalities of imaging and treatment, was prepared by encapsulating hypocrellin A, a photosensitive anti-cancer drug owned fluorescence, into the mesoporous silica nanoparticles. The results showed that after incorporation inside the mesoporous silica nanoparticles, the fluorescence intensity of hypocrellin A was greatly increased and the light stability was improved accordingly. Further more, comparative study of free hypocrellin A and the incorporated one indicated that both of them can be taken up by cancer cells, but the fluorescence of the incorporated one was more obvious and stable than the free one. Besides, significant damage to such impregnated tumor cells, treated with hypocrellin A incorporated mesoporous silica nanoparticles, was observed upon irradiation with light. Above results showed that such mesoporous silica nanoparticles with incorporated hypocrellin A have great application potential in the field of fluorescence imaging based diagnose and photodynamic therapy.
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