ARTICLE pubs.acs.org/ac
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 Yuka Takasaki,†,‡ Masaki Watanabe,‡ Hiroshi Yukawa,§ Akhmad Sabarudin,† Kazumi Inagaki,‡ Noritada Kaji,‡,|| Yukihiro Okamoto,‡,|| Manabu Tokeshi,‡,|| Yoshitaka Miyamoto,§ Hirofumi Noguchi,^ Tomonari Umemura,*,†,‡ Shuji Hayashi,§ Yoshinobu Baba,‡,||,# and Hiroki Haraguchi‡ †
Division of Nano-materials Science, EcoTopia Science Institute, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan § Department of Advanced Medicine in Biotechnology and Robotics, Graduate School of Medicine, Nagoya University, Higashi-ku, Nagoya 461-0047, Japan FIRST Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan ^ Baylor Institute for Immunology Research, Baylor Research Institute, 3434 Live Oak Street, Dallas, Texas 75204, United States # Health Research Institute, National Institute of Advanced Industrial Science and Technology, Hayashi-cho 2217-14, Takamatsu 761-0395, Japan
)
‡
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 wholebody 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 HNO3 and H2O2 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.
S
tem cells, which have the ability to self-renew and to differentiate into multiple cell lineages, have attracted much attention in the field of regenerative medicine.1 3 Among stem cells, adipose tissuederived stem cells (ASCs) are relatively easy to obtain from a patient by minimally invasive harvest procedures such as lipoaspiration with local anesthesia.4 Thus, ASCs are ideal candidates for use in r 2011 American Chemical Society
regenerative medicine,5 8 and our research group reported that ASCs injected intravenously exerted a curative influence on liver failure.9 Received: August 5, 2011 Accepted: September 29, 2011 Published: September 29, 2011 8252
dx.doi.org/10.1021/ac202053y | Anal. Chem. 2011, 83, 8252–8258
Analytical Chemistry
ARTICLE
Table 1. Operating Conditions of HR-ICPMS (ELEMENT 2) value Plasma Conditions radio frequency (rf)
27.12 MHz
incident rf power
1.2 kW
reflected power
