MagA increases MRI sensitivity and attenuates peroxidation-based damage to the bone-marrow haematopoietic microenvironment caused by iron overload

Artif Cells Nanomed Biotechnol. 2018;46(sup3):S18-S27. doi: 10.1080/21691401.2018.1489260. Epub 2018 Jul 22.

Abstract

Early evaluation of iron overload (IO) and prompt iron-chelation therapy reduce the haematopoietic damage wrought by IO-induced reactive oxygen species (ROS). We examined whether MagA could simultaneously increase the sensitivity of magnetic resonance imaging (MRI) for iron measurement and attenuate oxidative damage to the haematopoietic microenvironment. After generation of a transgenic (Tg) mouse model, MRI, transmission electron microscopy and cytotoxicity assays were used to assess various parameters in mesenchymal stem cells (MSCs). Transverse relaxation rate (R2*) of MagA-expressing MSCs in the presence of iron supplement was higher compared with that of control cells. Besides, R2* value of liver from IO magA Tg mice was higher than that of wild type mice. Moreover, MagA contributed to reduce the cytotoxicity of iron against MSCs, reduce expression of p-p38 mitogen-activated protein kinase and ferritin, and reduce inhibition of the osteogenic differentiation caused by IO. These data support the use of magA as a reporter gene for cell tracking with MRI and indicate exciting new possibilities for use of MagA in the attenuation of injury due to oxidative stress caused by exogenous iron.

Keywords: MagA; iron overload; magnetic resonance imaging; mesenchymal stem cell; reactive oxygen species.

MeSH terms

  • Animals
  • Bacterial Proteins* / biosynthesis
  • Bacterial Proteins* / genetics
  • Bone Marrow* / diagnostic imaging
  • Bone Marrow* / metabolism
  • Cation Transport Proteins* / biosynthesis
  • Cation Transport Proteins* / genetics
  • Genes, Reporter*
  • Hematopoiesis*
  • Iron / metabolism*
  • Iron Overload* / diagnostic imaging
  • Iron Overload* / genetics
  • Iron Overload* / metabolism
  • Magnetic Resonance Imaging*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Transgenic
  • Stem Cell Niche*

Substances

  • Bacterial Proteins
  • Cation Transport Proteins
  • MagA protein, Magnetospirillum
  • Iron