Comparative in vitro study on magnetic iron oxide nanoparticles for MRI tracking of adipose tissue-derived progenitor cells

PLoS One. 2014 Sep 22;9(9):e108055. doi: 10.1371/journal.pone.0108055. eCollection 2014.

Abstract

Magnetic resonance imaging (MRI) using measurement of the transverse relaxation time (R2*) is to be considered as a promising approach for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. While the relationship between core composition of nanoparticles and their MRI properties is well studied, little is known about possible effects on progenitor cells. This in vitro study aims at comparing two magnetic iron oxide nanoparticle types, single vs. multi-core nanoparticles, regarding their physico-chemical characteristics, effects on cellular behavior of adipose tissue-derived stem cells (ASC) like differentiation and proliferation as well as their detection and quantification by means of MRI. Quantification of both nanoparticle types revealed a linear correlation between labeling concentration and R2* values. However, according to core composition, different levels of labeling concentrations were needed to achieve comparable R2* values. Cell viability was not altered for all labeling concentrations, whereas the proliferation rate increased with increasing labeling concentrations. Likewise, deposition of lipid droplets as well as matrix calcification revealed to be highly dose-dependent particularly regarding multi-core nanoparticle-labeled cells. Synthesis of cartilage matrix proteins and mRNA expression of collagen type II was also highly dependent on nanoparticle labeling. In general, the differentiation potential was decreased with increasing labeling concentrations. This in vitro study provides the proof of principle for further in vivo tracking experiments of progenitor cells using nanoparticles with different core compositions but also provides striking evidence that combined testing of biological and MRI properties is advisable as improved MRI properties of multi-core nanoparticles may result in altered cell functions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Cell Differentiation
  • Female
  • Ferric Compounds / chemistry*
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Imaging
  • Magnetics*
  • Male
  • Metal Nanoparticles*
  • Stem Cells / cytology*

Substances

  • Ferric Compounds
  • ferric oxide

Grant support

The State Ministry of Economic Affairs, Employment, and Tourism of Mecklenburg-Vorpommern financially supported this work (V-630-S-083-2010/245) within the scope of a specific program which includes besides research institutions also local small and mid-sized companies. Both nanoparticle types were manufactured and provided by Micromod Partikeltechnologie GmbH. Dr. Grüttner characterized the nanoparticles in terms of hydrodynamic particle diameter, polydispersity index, and zeta potential which includes data collection and analysis as well as preparation of the manuscript.