Encapsulin Based Self-Assembling Iron-Containing Protein Nanoparticles for Stem Cells MRI Visualization

Int J Mol Sci. 2021 Nov 12;22(22):12275. doi: 10.3390/ijms222212275.

Abstract

Over the past decade, cell therapy has found many applications in the treatment of different diseases. Some of the cells already used in clinical practice include stem cells and CAR-T cells. Compared with traditional drugs, living cells are much more complicated systems that must be strictly controlled to avoid undesirable migration, differentiation, or proliferation. One of the approaches used to prevent such side effects involves monitoring cell distribution in the human body by any noninvasive technique, such as magnetic resonance imaging (MRI). Long-term tracking of stem cells with artificial magnetic labels, such as magnetic nanoparticles, is quite problematic because such labels can affect the metabolic process and cell viability. Additionally, the concentration of exogenous labels will decrease during cell division, leading to a corresponding decrease in signal intensity. In the current work, we present a new type of genetically encoded label based on encapsulin from Myxococcus xanthus bacteria, stably expressed in human mesenchymal stem cells (MSCs) and coexpressed with ferroxidase as a cargo protein for nanoparticles' synthesis inside encapsulin shells. mZip14 protein was expressed for the enhancement of iron transport into the cell. Together, these three proteins led to the synthesis of iron-containing nanoparticles in mesenchymal stem cells-without affecting cell viability-and increased contrast properties of MSCs in MRI.

Keywords: cell tracking; encapsulins; magnetic resonance imaging.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Ceruloplasmin / genetics
  • Ceruloplasmin / metabolism
  • Humans
  • Iron / chemistry*
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Myxococcus xanthus / genetics
  • Myxococcus xanthus / metabolism

Substances

  • Bacterial Proteins
  • Cation Transport Proteins
  • Magnetite Nanoparticles
  • SLC39A14 protein, mouse
  • Iron
  • Ceruloplasmin