Novel positively charged nanoparticle labeling for in vivo imaging of adipose tissue-derived stem cells

PLoS One. 2014 Nov 3;9(11):e110142. doi: 10.1371/journal.pone.0110142. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Cell Tracking / methods*
  • Cytokines / biosynthesis
  • Female
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles / chemistry
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Staining and Labeling*
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Cytokines
  • Magnetite Nanoparticles

Grants and funding

This research was supported by the Cabinet Office, Government of Japan and the Japan Society for the Promotion of Science (JSPS) through the Funding Program for World- Leading Innovative R& D on Science and Technology (FIRST Program) and partially supported by the Japan Science and Technology Agency (JST) through its “Research Center Network for Realization of Regenerative Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.