Optical bioluminescence imaging of human ES cell progeny in the rodent CNS Journal Article

Authors: Bradbury, M. S.; Panagiotakos, G.; Chan, B. K.; Tomishima, M.; Zanzonico, P.; Vider, J.; Ponomarev, V.; Studer, L.; Tabar, V.
Article Title: Optical bioluminescence imaging of human ES cell progeny in the rodent CNS
Abstract: Pre-clinical efforts of grafting human embryonic stem cell (hESC)-derived neural precursors have been hampered by problems ranging from graft rejection to overgrowth and tumor formation. The ability to detect such potential complications sensitively and reliably in clinically relevant contexts will rest upon the implementation of suitable non-invasive imaging technologies for continuously probing graft survival, proliferation, and migration. Neural precursors were transduced ex vivo using a lentiviral-mediated gene delivery system expressing firefly d-luciferase, under the control of a cytomegalovirus promoter. Transduced cells revealed no loss of cellular morphology, proliferative capacity, or neural phenotype in vitro. As a novel approach to monitoring the fate of human grafts within the living brain, we adapted optical bioluminescence imaging to assess long-term graft viability in immunodeficient mouse models transplanted with genetically engineered human neural precursor cells. We additionally applied this technology to immunocompetent models for detecting and characterizing the time course of graft rejection. Using this strategy, we define statistically relevant imaging criteria that can predict graft rejection or overgrowth. In conclusion, our data suggest that optical bioluminescence imaging can serve as an essential tool for the development of hESC-based grafting strategies in the CNS. © 2007 The Authors.
Keywords: nonhuman; cell proliferation; animal cell; mouse; animals; mice; animal tissue; cell viability; cells, cultured; embryonic stem cell; fluorescent dyes; animal model; stem cell transplantation; in vivo study; in vitro study; mice, scid; central nervous system; genetic transduction; genetic vectors; imaging system; genetic engineering; long term care; transplantation, heterologous; embryonic stem cells; green fluorescent proteins; microscopy, fluorescence; rodentia; graft rejection; graft survival; immune deficiency; luciferases; optics; bioluminescence; cytomegalovirus; immunocompetence; corpus striatum; gene transfer techniques; xenografts; optical imaging; bli; cns transplantation; human es cell grafts; brain graft; chemiluminescent measurements
Journal Title: Journal of Neurochemistry
Volume: 102
Issue: 6
ISSN: 0022-3042
Publisher: Wiley Blackwell  
Date Published: 2007-09-01
Start Page: 2029
End Page: 2039
Language: English
DOI: 10.1111/j.1471-4159.2007.04681.x
PUBMED: 17555555
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: JONRA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Viviane S Tabar
    145 Tabar
  2. Vladimir Ponomarev
    103 Ponomarev
  3. Lorenz Studer
    167 Studer
  4. Pat B Zanzonico
    282 Zanzonico
  5. Jelena Vider
    31 Vider
  6. Bill Chan
    4 Chan