title: 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.
authors.affiliation: Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yukawa
authors.affiliation: Department of Medical Technology, Nagoya University, Graduate School of Medicine, Daikominami, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Medical Technology, Nagoya University, Graduate School of Medicine, Daikominami, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Yasuma
authors.initials: Y
authors.lastname: Yoshizumi
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Nagoya Research Laboratory, MEITO Sangyo Co., Ltd., Kiyosu 452-0067, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Advanced Medicine in Biotechnology and Robotics, Graduate School of Medicine, Nagoya University, Higashi-ku, Nagoya 461-0047, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Research Institute of Environmental Medicine, Stress Adaption and Protection, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Research Institute of Environmental Medicine, Stress Adaption and Protection, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ono
authors.affiliation: Research Institute of Environmental Medicine, Stress Adaption and Protection, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.affiliation: Nagoya Research Laboratory, MEITO Sangyo Co., Ltd., Kiyosu 452-0067, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kato
authors.affiliation: Institute of Innovative for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Onoshima
authors.affiliation: Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Obayashi
authors.affiliation: Department of Medical Technology, Nagoya University, Graduate School of Medicine, Daikominami, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Research Center for Innovative Nanobiodevices, 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.
authors.forename: Noritada
authors.initials: N
authors.lastname: Kaji
authors.affiliation: Department of Medical Technology, Nagoya University, Graduate School of Medicine, Daikominami, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Advanced Medicine in Biotechnology and Robotics, Graduate School of Medicine, Nagoya University, Higashi-ku, Nagoya 461-0047, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Research Center for Innovative Nanobiodevices, 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; Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Hayashi-cho 2217-14, Takamatsu 761-0395, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Baba
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013194:Staining and Labeling; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D058185:Magnetite Nanoparticles