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Variability in contrast agent uptake by different but similar stem cell types.

ABSTRACT: The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200) to label relatively larger, mesenchymal stem cells (MSCs) and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs). Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high-resolution electron microscopy images, demonstrated a strong relationship between cell volume/surface, uptake, and cytotoxicity. Interestingly, uptake and toxicity trends are reversed if intracellular concentrations, and not amounts, are considered. This indicates that more attention should be paid to cellular parameters such as cell size and proliferation rate in comparative cell-labeling studies.

SUBMITTER: Ketkar-Atre A

PROVIDER: S-EPMC3876490 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Variability in contrast agent uptake by different but similar stem cell types.

Ketkar-Atre Ashwini A Struys Tom T Soenen Stefaan J SJ Lambrichts Ivo I Verfaillie Catherine M CM De Cuyper Marcel M Himmelreich Uwe U

International journal of nanomedicine 20131129

The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we h ...[more]

PMID: 24399873

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Project description:(1) Background: We recently showed that iodinated contrast media (ICM) reduced thyroid uptake of iodide independently of free iodide through a mechanism different from that of NaI and involving a dramatic and long-lasting decrease in Na/I symporter expression. The present study aimed at comparing the response of the thyroid to ICM and NaI using a quantitative proteomic approach. (2) Methods: Scintiscans were performed on ICM-treated patients. Micro Single-Photon Emission Computed Tomography (microSPECT/CT) imaging was used to assess thyroid uptakes in ICM- or NaI-treated mice and their response to recombinant human thyroid-stimulating hormone. Total thyroid iodide content and proteome was determined in control, NaI-, or ICM-treated animals. (3) Results: The inhibitory effect of ICM in patients was selectively observed on thyroids but not on salivary glands for up to two months after a systemic administration. An elevated level of iodide was observed in thyroids from NaI-treated mice but not in those from ICM animals. Exposure of the thyroid to NaI modulates 15 cellular pathways, most of which are also affected by ICM treatment (including the elF4 and P706SK cell signaling pathway and INSR identified as an upstream activator in both treatments). In addition, ICM modulates 16 distinct pathways and failed to affect thyroid iodide content. Finally, administration of ICM reduces thyroid-stimulating hormone (TSH) receptor expression which results in a loss of TSH-induced iodide uptake by the thyroid. (4) Conclusions: Common intracellular mechanisms are involved in the ICM- and NaI-induced reduction of iodide uptake. However, ICM fails to affect thyroid iodide content which suggests that the modulation of these common pathways is triggered by separate effectors. ICM also modulates numerous distinct pathways which may account for its long-lasting effect on thyroid uptake. These observations may have implications in the management of patients affected by differentiated thyroid carcinomas who have been exposed to ICM. They also provide the basis for the utilization of ICM-based compounds in radioprotection of the thyroid.

Project description:BackgroundComparative studies of the associations between different infectious diseases and climate variability, such as the El Niño-Southern Oscillation, are lacking. Diarrheal illnesses, particularly cholera and shigellosis, provide an important opportunity to apply a comparative approach. Cholera and shigellosis have significant global mortality and morbidity burden, pronounced differences in transmission pathways and pathogen ecologies, and there is an established climate link with cholera. In particular, the specific ecology of Vibrio cholerae is often invoked to explain the sensitivity of that disease to climate.Methods and findingsThe extensive surveillance data of the International Center for Diarrheal Disease Research, Bangladesh are used here to revisit the known associations between cholera and climate, and to address their similarity to previously unexplored patterns for shigellosis. Monthly case data for both the city of Dhaka and a rural area known as Matlab are analyzed with respect to their association with El Niño and flooding. Linear correlations are examined between flooding and cumulative cases, as well as for flooding and El Niño. Rank-correlation maps are also computed between disease cases in the post-monsoon epidemic season and sea surface temperatures in the Pacific. Similar climate associations are found for both diseases and both locations. Increased cases follow increased monsoon flooding and increased sea surface temperatures in the preceding winter corresponding to an El Niño event.ConclusionsThe similarity in association patterns suggests a systemic breakdown in population health with changing environmental conditions, in which climate variability acts primarily through increasing the exposure risk of the human population. We discuss these results in the context of the on-going debate on the relative importance of the environmental reservoir vs. secondary transmission, as well as the implications for the use of El Niño as an early indicator of flooding and enteric disease risk.

Project description:To propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast-enhanced (DCE) examinations undertaken with standard clinical fat-suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas.A standard fat-suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)-weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre-, peak-, and post-contrast agent administration) for 20 patients, pre-treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank-sum test).The calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat-suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre-, peak-, and post-contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post-contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post-contrast T1 values, potentially related to their infiltrative growth pattern.This work has demonstrated the feasibility of fat-suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.

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Variability in contrast agent uptake by different but similar stem cell types.

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Variability in contrast agent uptake by different but similar stem cell types.

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