Estimation of the Distribution of Intravenously Injected Adipose Tissue-Derived Stem Cells Labeled with Quantum Dots in Mice Organs through the Determination of their Metallic Components by ICPMS

Abstract

Adipose tissue-derived stem cells (ASCs) have shown promise in cell therapy because of their ability to self-renew damaged or diseased organs and easy harvest. To ensure the distribution and quantification of the ASCs injected from tail vein, several whole-body imaging techniques including fluorescence optical imaging with quantum dots (QDs) have been employed, but they may suffer from insufficient sensitivity and accuracy. Here, we report quantitative distribution of ASCs in various organs (heart, lung, liver, spleen, and kidney) of mice, which were intravenously injected with QDs-labeled ASCs (QDs-ASCs), through the detection of QDs-derived metallic components by inductively coupled plasma mass spectrometry (ICPMS). For accurate and precise determination, each organ was harvested and completely digested with a mixture of HNO(3) and H(2)O(2) in a microwave oven prior to ICPMS measurement, which was equipped with a microflow injection system and a laboratory-made capillary-attached micronebulizer. After optimization, 16 elements including major components (Cd, Se, and Te) of QDs and essential elements (Na, K, Mg, Ca, P, S, Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo) were successfully determined in the organs. As compared to untreated mice, QDs-ASCs-treated mice showed significantly higher levels of Cd and Te in all organs, and as expected, the molar ratio of Cd to Te in each organ was in good agreement with the molar composition ratio in the QDs. This result indicates that the increment of Cd (or Te) can be used as a tracer for calculating the distribution of ASCs in mice organs. As a result of the calculation, 36.8%, 19.1%, 0.59%, 0.49%, and 0.25% of the total ASCs injected were estimated to be distributed in the liver, lung, heart, spleen, and kidney, respectively.

Intravenous administration of adipose-derived stromal cells does not ameliorate bleomycin-induced lung injury in rats

“…With regard to cell transplantation into the lungs, some authors have investigated the survival rate of intravenously administerd MSCs, and found high percentages [29][30][31]. Because the duration from MSC injection to estimation of the cell counts in these studies was much shorter than the 3 and 6 weeks used in our study, our cell survival rate cannot be directly compared with the previous reports.…”

Elemental labelling combined with liquid chromatography inductively coupled plasma mass spectrometry for quantification of biomolecules: A review

“…Another FI-ICP-MS approach published by Takasaki et al [115] employed quantum dots (QD) with a Cd, Te and Se bearing core for elemental labelling of adipose tissue-derived stem cells. Due to the small sample size (approximately 1 mg) an optimized microwave assisted acid digestion procedure was developed.…”

ICP–MS in Drug Development: High-Throughput Analysis of Strontium and Calcium in Bone, Tissue and Plasma

“…The tissue distribution of these samples is shown in Figure 5. All analyses were performed in a period of 12 Figure 7. Effect of exposure to esomeprazole strontium tetrahydrate and esomeprazole magnesium trihydrate on strontium and calcium in femur from adult and fetal rats.…”

“…Typically, an acidic or basic sample digestion is used either with the assistance of microwaves [7][8][9][10][11][12] or heating [13,14]. Although microwave digestion has a pronounced advantage in terms of speed of sample preparation, microwave treatment cannot be performed in a highly parallel manner, thereby strongly limiting sample throughput.…”