Tracking of Adipose-Derived Mesenchymal Stromal/Stem Cells in a Model of Cisplatin-Induced Acute Kidney Injury: Comparison of Bioluminescence Imaging versus qRT-PCR

Int J Mol Sci. 2018 Aug 29;19(9):2564. doi: 10.3390/ijms19092564.

Abstract

Determining the cell fate and the distribution of mesenchymal stromal/stem cells (MSCs) after transplantation are essential parts of characterizing the mechanisms of action and biosafety profile of stem cell therapy. Many recent studies have shown that MSCs migrate into injured tissues, but are only detectable at extremely low frequencies. We investigated the cell fate of MSCs after transplantation in an acute kidney injury (AKI) mouse model using in vivo bioluminescence imaging (BLI) and subsequent verification of cell migration using quantitative real-time polymerase chain reaction (qRT-PCR). The AKI was induced by a single injection of cisplatin (8 or 12 mg/kg). One day later, adipose-derived mesenchymal stromal/stem cells isolated from luciferase transgenic mice (Luc⁺-mASCs, 5 × 10⁵) were intravenously transplanted. Migration kinetics of the cells was monitored using BLI on day 1, 3, and 6, and finally via quantitative real-time PCR at the endpoint on day 6. Using BLI, infused Luc⁺-mASCs could only be detected in the lungs, but not in the kidneys. In contrast, PCR endpoint analysis revealed that Luc-specific mRNA could be detected in injured renal tissue; compared to the control group, the induction was 2.2-fold higher for the 8 mg/kg cisplatin group (p < 0.05), respectively 6.1-fold for the 12 mg/kg cisplatin group (p < 0.001). In conclusion, our study demonstrated that Luc-based real-time PCR rather than BLI is likely to be a better tool for cell tracking after transplantation in models such as cisplatin-induced AKI.

Keywords: PCR; acute kidney injury; bio imaging; bioluminescence; mesenchymal stromal/stem cells; qRT-PCR; renal failure; tracking.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / therapy
  • Animals
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Cisplatin / adverse effects*
  • Disease Models, Animal
  • Luminescent Measurements
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Real-Time Polymerase Chain Reaction
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / therapy*
  • Stem Cell Transplantation

Substances

  • Cisplatin