Feasibility of baculovirus-mediated reporter gene delivery for efficient monitoring of islet transplantation in vivo

Nucl Med Biol. 2014 Feb;41(2):171-8. doi: 10.1016/j.nucmedbio.2013.10.009. Epub 2013 Oct 29.

Abstract

Objective: The objective of this study was to explore the feasibility of baculovirus vector-mediated sodium iodide symporter (NIS) gene delivery to monitor islet transplantation.

Methods: Baculovirus vectors expressing green fluorescent protein (GFP) or NIS (Bac-GFP and Bac-NIS) were established using the Bac-to-Bac baculovirus expression system. The GFP expression of Bac-GFP-infected rat islets was observed in vitro by fluorescence microscopy. Iodine uptake and inhibition of iodine uptake by NaClO4 in Bac-NIS-infected islets were dynamically monitored in vitro. Bac-GFP- or Bac-NIS-infected islets were implanted into the left axillary cavity of NOD-SCID mice, and fluorescence imaging and (125)I NanoSPECT/CT imaging were subsequently performed in vivo.

Results: Bac-GFP efficiently infected rat islets (over 95% infected at MOI=40), and the expression of GFP lasted approximately two weeks. NaClO4 could inhibit iodine uptake by Bac-NIS-infected islets. In vivo imaging revealed that the fluorescence intensity of the transplant sites in Bac-GFP-infected groups was significantly higher than in the non-infected group. Grafts could be clearly observed by (125)I NanoSPECT/CT imaging for up to 8 h.

Conclusion: Baculovirus vectors are powerful vehicles for studying rat islets in gene delivery. It is feasible to use a baculovirus vector to delivery an NIS gene for non-invasive monitoring transplanted islets in vivo by the expression of the target gene.

Keywords: Baculovirus; Islet; Molecular imaging; Sodium iodine symporter; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics*
  • Biological Transport
  • Feasibility Studies
  • Genes, Reporter / genetics*
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins / genetics
  • Iodine / metabolism
  • Islets of Langerhans / cytology
  • Islets of Langerhans / diagnostic imaging
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation*
  • Male
  • Mice
  • Rats
  • Symporters / genetics
  • Tissue Survival
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • Transduction, Genetic / methods*
  • Treatment Outcome

Substances

  • Symporters
  • Green Fluorescent Proteins
  • sodium-iodide symporter
  • Iodine