Mesenchymal stromal cells (MSCs) are currently under investigation for the treatment of inflammatory disorders, including Crohn's disease. MSCs are pluripotent cells with immunosuppressive... Show moreMesenchymal stromal cells (MSCs) are currently under investigation for the treatment of inflammatory disorders, including Crohn's disease. MSCs are pluripotent cells with immunosuppressive properties. Recent data suggest that resting MSCs do not have significant immunomodulatory activity, but that the immunosuppressive function of MSCs has to be elicited by interferon-gamma (IFN-gamma). In this article, we assessed the effects of IFN-gamma prestimulation of MSCs (IMSCs) on their immunosuppressive properties in vitro and in vivo. To this end, we pretreated MSCs with IFN-gamma and assessed their therapeutic effects in dextran sodium sulfate (DSS)- and trinitrobenzene sulfonate (TNBS)-induced colitis in mice. We found that mice treated with IMSCs (but not MSCs) showed a significantly attenuated development of DSS-induced colitis. Furthermore, IMSCs alleviated symptoms of TNBS-induced colitis. IMSC-treated mice displayed an increase in body weight, lower colitis scores, and better survival rates compared with untreated mice. In addition, serum amyloid A protein levels and local proinflammatory cytokine levels in colonic tissues were significantly suppressed after administration of IMSC. We also observed that IMSCs showed greater migration potential than unstimulated MSCs to sites within the inflamed intestine. In conclusion, we show that prestimulation of MSCs with IFN-gamma enhances their capacity to inhibit Th1 inflammatory responses, resulting in diminished mucosal damage in experimental colitis. These data demonstrate that IFN-gamma activation of MSCs increases their immunosuppresive capacities and importantly, their therapeutic efficacy in vivo. STEM CELLS 2011;29:1549-1558 Show less
Studies on stem cell are rapidly developing since these cells have great therapeutic potential for numerous diseases and has generated much promise as well as confusion due to contradictory results... Show moreStudies on stem cell are rapidly developing since these cells have great therapeutic potential for numerous diseases and has generated much promise as well as confusion due to contradictory results. Major questions in this research field have been raised as to how and in which numbers stem cells home to target tissues after administration, whether the cells engraft and differentiate, and what their long-term fate is. To answer these questions, reliable in vivo tracking techniques are essential. In vivo molecular imaging techniques using magnetic resonance imaging, bioluminescence, and scintigraphy have been applied for this purpose in experimental studies. The aim of this review is to discuss various radiolabeling techniques for early stem cell tracking, the need for validation of viability and performance of the cells after labeling, and the routes of administration in experimental animal models. In addition, we evaluate current problems and directions related to stem cell tracking using radiolabels, including a possible role for their clinical implementation. J. Cell. Physiol. 226: 1444-1452, 2011. (C) 2010 Wiley-Liss, Inc. Show less
Welling, M.M.; Duijvestein, M.; Signore, A.; Weerd, L. van der 2010
AIM The aim of this paper was to test the ability of technetium-99m labelled synthetic peptide UBI 29-41 scintigraphy (99mTc-UBI 29-41), composed of the antimicrobial peptide ubiquicidin,... Show moreAIM The aim of this paper was to test the ability of technetium-99m labelled synthetic peptide UBI 29-41 scintigraphy (99mTc-UBI 29-41), composed of the antimicrobial peptide ubiquicidin, specifically targets microorganisms in to discriminate between infected and uninfected endocarditis using a rat model previously validated. METHODS 99mTc-UBI 29-41 scintigraphy was evaluated for its accumulation in infective endocarditis (IE) with multidrug resistant Staphylococcus aureus (MRSA) performed in an experimental rat model, resembling early endocarditis in humans. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. Heart-to-lung uptake ratios (T/NT ratios) were calculated in both with in-vivo scintigraphy and in ex vivo tissue samples. RESULTS Bacterially infected vegetations were already observed at 15 min after injection of 99mTc-UBI 29-41 while no significant uptake was observed in sterile vegetations. Moreover, a good correlation (R2=0.819) was calculated between T/NT ratios of 99mTc-UBI 29-41 and the number of viable MRSA present in the infected vegetation. There was no correlation between the 99mTc-UBI 29-41 uptake and the weight of the vegetations in either case. CONCLUSION In this experimental study in rats, planar 99mTc-UBI 29-41 scintigraphy permitted early and specific detection of MRSA induced endocarditis. Furthermore, accumulation of the tracer depends on the number of viable MRSA and not on the weight of the vegetation. This proof of principle offers much promise that 99mTc-UBI 29-41 scintigraphy can be a dedicated non-invasive imaging tool for the early detection of infective endocarditis. Finally, this model has to be further evaluated with state-of-the art small imaging modalities. Show less
Aim. The aim of this paper was to test the ability of technetium-99m labelled synthetic peptide UBI 29-41 scintigraphy (Tc-99m-UBI 29-41), composed of the antimicrobial peptide ubiquicidin,... Show moreAim. The aim of this paper was to test the ability of technetium-99m labelled synthetic peptide UBI 29-41 scintigraphy (Tc-99m-UBI 29-41), composed of the antimicrobial peptide ubiquicidin, specifically targets microorganisms in to discriminate between infected and uninfected endocarditis using a rat model previously validated. Methods. Tc-99m-UBI 29-41 scintigraphy was evaluated for its accumulation in infective endocarditis (LE) with multidrug resistant Staphylococcus aureus (MRSA) performed in an experimental rat model, resembling early endocarditis in humans. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. Heart-to-lung uptake ratios (T/NT ratios) were calculated in both with in-vivo scintigraphy and in ex vivo tissue samples. Results. Bacterially infected vegetations were already observed at 15 min after injection of Tc-99m-UBI 29-41 while no significant uptake was observed in sterile vegetations. Moreover, a good correlation (R-2=0.819) was calculated between T/NT ratios of Tc-99m-UBI 29-41 and the number of viable MRSA present in the infected vegetation. There was no correlation between the Tc-99m-UBI 2941 uptake and the weight of the vegetations in either case. Conclusion. In this experimental study in rats, planar Tc-99m-UBI 29-41 scintigraphy permitted early and specific detection of MRSA induced endocarditis. Furthermore, accumulation of the tracer depends on the number of viable MRSA and not on the weight of the vegetation. This proof of principle offers much promise that Tc-99m-UBI 29-41 scintigraphy can be a dedicated non-invasive imaging tool for the early detection of infective endocarditis. Finally, this model has to be further evaluated with state-of-the art small imaging modalities. Show less
OBJECTIVE: The aim of this study was to investigate the differences in biological performance between a technetium-99m (Tc)-labelled glucose derivative, the Tc-labelled 1-thio-beta-D-glucose 2,3,4... Show moreOBJECTIVE: The aim of this study was to investigate the differences in biological performance between a technetium-99m (Tc)-labelled glucose derivative, the Tc-labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate analogue (Tc-TG) with F-fluoro-2-deoxy-glucose ([F]FDG). METHODS: Binding of both tracers was performed in vitro to viable tumour cells and bacteria. Both tracers were injected into mice for targeting Staphylococcus aureus thigh muscle infections and subcutaneous rat lymphoma (RMA) tumours by using scintigraphy, or by radioactivity counts in excised tissues to determine the biodistribution. RESULTS: In-vitro binding studies revealed that both tracers bind more effectively to tumour cells expressing the glucose transporter 1 rather than the glucose transporter 2, and this binding was specific for [F]FDG. Tc-TG shows the highest binding to bacteria and, in addition, gives the highest rate of accumulation in infected thigh muscles in mice. Both tracers were rapidly removed from the circulatory system through the kidneys, and the majority of the injected radioactivity accumulated in the urinary bladder. Two hours after the injection radioactivity accumulation in two high-energy-dependent organs, heart, and liver, increased. Within 15 min of the injections, Tc-TG visualized the site of S. aureus infection or the tumour. CONCLUSION: We conclude that the new tracer Tc-TG may have potential use as a SPECT agent for infection and tumour imaging. Show less
Objective The aim of this study was to investigate the differences in biological performance between a technetium-99m (Tc-99m)-labelled glucose derivative, the Tc-99m-labelled 1-thio-beta-D-glucose... Show moreObjective The aim of this study was to investigate the differences in biological performance between a technetium-99m (Tc-99m)-labelled glucose derivative, the Tc-99m-labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate analogue (Tc-99m-TG) with F-18-fluoro-2-deoxy-glucose ([F-18]FDG). Methods Binding of both tracers was performed in vitro to viable tumour cells and bacteria. Both tracers were injected into mice for targeting Staphylococcus aureus thigh muscle infections and subcutaneous rat lymphoma (RMA) tumours by using scintigraphy, or by radioactivity counts in excised tissues to determine the biodistribution. Results In-vitro binding studies revealed that both tracers bind more effectively to tumour cells expressing the glucose transporter 1 rather than the glucose transporter 2, and this binding was specific for [F-18]FDG. (99)mTc-TG shows the highest binding to bacteria and, in addition, gives the highest rate of accumulation in infected thigh muscles in mice. Both tracers were rapidly removed from the circulatory system through the kidneys, and the majority of the injected radioactivity accumulated in the urinary bladder. Two hours after the injection radioactivity accumulation in two high-energy-dependent organs, heart, and liver, increased. Within 15 min of the injections, Tc-99m-TG visualized the site of S. aureus infection or the tumour. Conclusion We conclude that the new tracer Tc-99m-TG may have potential use as a SPECT agent for infection and tumour imaging. Nucl Med Commun 31: 239-248 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Show less
![Performance of a 99mTc-labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate analogue in the detection of infections and tumours in mice: a comparison with [18F]FDG](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=9dc17a3d2098a8a26bc4&solr_nav%5Bpage%5D=2&solr_nav%5Boffset%5D=9)
![Performance of a Tc-99m-labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate analogue in the detection of infections and tumours in mice: a comparison with [F-18]FDG](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=9dc17a3d2098a8a26bc4&solr_nav%5Bpage%5D=2&solr_nav%5Boffset%5D=10)
