RT Journal Article
SR Electronic
T1 Molecular Imaging of Human Embryonic Stem Cells Stably Expressing Human PET Reporter Genes After Zinc Finger Nuclease–Mediated Genome Editing
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1659
OP 1665
DO 10.2967/jnumed.117.189779
VO 58
IS 10
A1 Esther Wolfs
A1 Bryan Holvoet
A1 Laura Ordovas
A1 Natacha Breuls
A1 Nicky Helsen
A1 Matthias Schönberger
A1 Susanna Raitano
A1 Tom Struys
A1 Bert Vanbilloen
A1 Cindy Casteels
A1 Maurilio Sampaolesi
A1 Koen Van Laere
A1 Ivo Lambrichts
A1 Catherine M. Verfaillie
A1 Christophe M. Deroose
YR 2017
UL http://jnm.snmjournals.org/content/58/10/1659.abstract
AB Molecular imaging is indispensable for determining the fate and persistence of engrafted stem cells. Standard strategies for transgene induction involve the use of viral vectors prone to silencing and insertional mutagenesis or the use of nonhuman genes. Methods: We used zinc finger nucleases to induce stable expression of human imaging reporter genes into the safe-harbor locus adeno-associated virus integration site 1 in human embryonic stem cells. Plasmids were generated carrying reporter genes for fluorescence, bioluminescence imaging, and human PET reporter genes. Results: In vitro assays confirmed their functionality, and embryonic stem cells retained differentiation capacity. Teratoma formation assays were performed, and tumors were imaged over time with PET and bioluminescence imaging. Conclusion: This study demonstrates the application of genome editing for targeted integration of human imaging reporter genes in human embryonic stem cells for long-term molecular imaging.