In vivo tracking of human neural progenitor cells in the rat brain using bioluminescence imaging

J Neurosci Methods. 2014 May 15:228:67-78. doi: 10.1016/j.jneumeth.2014.03.005. Epub 2014 Mar 24.

Abstract

Background: Stem cell therapies appear promising for treating certain neurodegenerative disorders and molecular imaging methods that track these cells in vivo could answer some key questions regarding their survival and migration. Bioluminescence imaging (BLI), which relies on luciferase expression in these cells, has been used for this purpose due to its high sensitivity.

New method: In this study, we employ BLI to track luciferase-expressing human neural progenitor cells (hNPC(Luc2)) in the rat striatum long-term.

Results: We show that hNPC(Luc2) are detectable in the rat striatum. Furthermore, we demonstrate that using this tracking method, surviving grafts can be detected in vivo for up to 12 weeks, while those that were rejected do not produce bioluminescence signal. We also demonstrate the ability to discern hNPC(Luc2) contralateral migration.

Comparison with existing methods: Some of the advantages of BLI compared to other imaging methods used to track progenitor/stem cells include its sensitivity and specificity, low background signal and ability to distinguish surviving grafts from rejected ones over the long term while the blood-brain barrier remains intact.

Conclusions: These new findings may be useful in future preclinical applications developing cell-based treatments for neurodegenerative disorders.

Keywords: Bioluminescence; Human neural progenitor cells; Luciferase; Rat.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count
  • Cell Line, Transformed
  • Cell Movement
  • Corpus Striatum / cytology*
  • Corpus Striatum / surgery
  • Cyclosporine / pharmacology
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Luminescent Measurements*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / surgery
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology*
  • Neuroimaging / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation
  • Time Factors
  • Transfection

Substances

  • Nerve Tissue Proteins
  • Cyclosporine
  • Luciferases
  • Bromodeoxyuridine