Novel Positively Charged Nanoparticle Labeling for In Vivo Imaging of Adipose Tissue-Derived Stem Cells

Abstract

Stem cell transplantation has been expected to have various applications for regenerative medicine. However, in order to detect and trace the transplanted stem cells in the body, non-invasive and widely clinically available cell imaging technologies are required. In this paper, we focused on magnetic resonance (MR) imaging technology, and investigated whether the trimethylamino dextran-coated magnetic iron oxide nanoparticle -03 (TMADM-03), which was newly developed by our group, could be used for labeling adipose tissue-derived stem cells (ASCs) as a contrast agent. No cytotoxicity was observed in ASCs transduced with less than 100 µg-Fe/mL of TMADM-03 after a one hour transduction time. The transduction efficiency of TMADM-03 into ASCs was about four-fold more efficient than that of the alkali-treated dextran-coated magnetic iron oxide nanoparticle (ATDM), which is a major component of commercially available contrast agents such as ferucarbotran (Resovist), and the level of labeling was maintained for at least two weeks. In addition, the differentiation ability of ASCs labeled with TMADM-03 and their ability to produce cytokines such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2), were confirmed to be maintained. The ASCs labeled with TMADM-03 were transplanted into the left kidney capsule of a mouse. The labeled ASCs could be imaged with good contrast using a 1T MR imaging system. These data suggest that TMADM-03 can therefore be utilized as a contrast agent for the MR imaging of stem cells.

Transduction Function of a Magnetic Nanoparticle TMADM for Stem-Cell Imaging with Quantum Dots

“…In a previous study, TMADM-03 was proven to be an effective contrast agent. 23 The transduction efficiency of TMADM-03 into ASCs was about four-fold more efficient than that of the alkali-treated dextran-coated magnetic iron oxide nanoparticle (ATDM), which is a major component of commercially available contrast agents, such as ferucarbotran. The labeled ASCs could be imaged with good contrast using a 1T MR imaging system in mice.…”

“…The labeled ASCs could be imaged with good contrast using a 1T MR imaging system in mice. 23 To investigate whether QDs655 can be transduced into ASCs using TMADM-03, ASCs were incubated with QDs655 using TMADM-03. Fluorescence images of ASCs incubated with QDs655 only and using TMADM-03 are shown in Figs.…”

“…17,23 On the other hand, QDs655 appears to be negatively charged, so appeared to interact with TMADM-03 due to the electrostatic force. As a result, TMADM-03 seems to serve as a transduction agent for QDs655.…”

“…16,17 We have already reported that TMADM-03 could label hepatocellular carcinoma cells (HepG2; liver hepatocellular carcinoma-derived cell line) 18 and ASCs. 23 TMADM-03 can transduce into cells through the cell membrane with high efficiency, and is therefore expected to serve as a transduction agent for various kinds of functional molecules. QDs are inorganic fluorescence probes that have many distinctive advantages in comparison to organic or protein fluorescence probes, including high luminance, superior photostability, high quantum yields and wide excitation wavelengths.…”

Physicochemical Properties of Magnetic Nanoparticles: Implications for Biomedical Applications In Vitro and In Vivo

“…Magnetic nanoparticles (MNPs) or superparamagnetic iron oxide nanoparticles (SPIONs) are emerging as promising candidates for applications in biomedicine for drug delivery [1][2][3], magnetic resonance imaging (MRI) [1,3], and hyperthermia-based therapy, in research projects encompassing cell mechanics, tumor progression dynamics, in vivo tracking of stem cells [4][5][6], and in general molecular and cell biology for nucleic acid isolation and cell separation [7]. This is all due to their ultra-fine and tunable size, notable biocompatibility, and superparamagnetic behavior.…”