title: Combination of cell delivery and thermoinducible transcription for in vivo spatiotemporal control of gene expression: a feasibility study.
abstract: OBJECTIVE
  To demonstrate the feasibility of combining in situ delivery of genetically modified cells into the rat kidney, to induce expression of a reporter gene under transcriptional control of a heat-inducible promoter activated with magnetic resonance (MR)-guided focused ultrasonography (US), and to demonstrate in vivo the local expression of the synthesized protein.
  
  
  METHODS
  Experiments were conducted in agreement with the European Commission guidelines and directives of the French Research Ministry. C6 cells were genetically modified by incorporating the firefly luciferase (LucF) gene under transcriptional control of a heat-sensitive promoter (human heat shock protein 70B). Engineered cells were injected in the renal artery of a superficialized left kidney (15 rats). Two days later, intrarenal LucF expression was induced noninvasively by local hyperthermia in 15 renal locations in nine rats with focused US and was controlled with MR temperature imaging. Six hours after heating, LucF activity was detected in vivo with bioluminescence imaging.
  
  
  RESULTS
  The genetically engineered C6 cell line was characterized in vitro for LucF expression related to the heating parameters. Changes in renal morphology and hemodynamic parameters as a result of rat kidney superficialization were not significant. Intrarenal temperature measurement at the focal point followed the scheduled temperature in 13 of 15 cases. On bioluminescence images, LucF activity was present only in heated regions. The level of LucF expression was also dependent on heating parameters. Substantial tissue damage was noted at histologic analysis in only the two cases in which temperature control was inadequate.
  
  
  CONCLUSIONS
  A strategy combining cell delivery of a transgene and a thermosensitive promoter that can be locally activated with MR-guided focused US is able to induce in vivo gene expression controlled in space and time.
  
  
  BACKGROUND
  http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100767/-/DC1.
authors.affiliation: Laboratory for Molecular and Functional Imaging, UMR5231 CNRS/University Victor Segalen Bordeaux, 146 rue Leo Saignat, 33076 Bordeaux, France.
authors.forename: Omer F
authors.initials: OF
authors.lastname: Eker
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesson
authors.forename: Claire
authors.initials: C
authors.lastname: Rome
authors.forename: Josette
authors.initials: J
authors.lastname: Arsaut
authors.forename: Colette
authors.initials: C
authors.lastname: Deminière
authors.forename: Chrit T
authors.initials: CT
authors.lastname: Moonen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Grenier
authors.forename: Franck
authors.initials: F
authors.lastname: Couillaud
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005240:Feasibility Studies; D015870:Gene Expression; D017930:Genes, Reporter; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007668:Kidney / Q000166:cytology* / Q000000981:diagnostic imaging* / Q000201:enzymology; D008156:Luciferases / Q000235:genetics*; D053783:Magnetic Resonance Imaging, Interventional; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013696:Temperature; D019076:Transgenes; D014463:Ultrasonography
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008156:Luciferases