A novel molecule integrating therapeutic and diagnostic activities reveals multiple aspects of stem cell-based therapy.

Stem Cells
Shawn HingtgenKhalid Shah

Abstract

Stem cells are promising therapeutic delivery vehicles; however pre-clinical and clinical applications of stem cell-based therapy would benefit significantly from the ability to simultaneously determine therapeutic efficacy and pharmacokinetics of therapies delivered by engineered stem cells. In this study, we engineered and screened numerous fusion variants that contained therapeutic (TRAIL) and diagnostic (luciferase) domains designed to allow simultaneous investigation of multiple events in stem cell-based therapy in vivo. When various stem cell lines were engineered with the optimized molecule, SRL(O)L(2)TR, diagnostic imaging showed marked differences in the levels and duration of secretion between stem cell lines, while the therapeutic activity of the molecule showed the different secretion levels translated to significant variability in tumor cell killing. In vivo, simultaneous diagnostic and therapeutic monitoring revealed that stem cell-based delivery significantly improved pharmacokinetics and anti-tumor effectiveness of the therapy compared to intravenous or intratumoral delivery. As treatment for highly malignant brain tumor xenografts, tracking SRL(O)L(2)TR showed stable stem cell-mediated delivery significantly re...Continue Reading

References

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Citations

Dec 18, 2012·Journal of Neuro-oncology·Shawn HingtgenKhalid Shah
Oct 1, 2013·Trends in Molecular Medicine·Daniel W Stuckey, Khalid Shah
Apr 12, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jong Min LeeGun-Il Im
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jeroen A J M van de WaterKhalid Shah
Jul 12, 2011·Advanced Drug Delivery Reviews·Khalid Shah
Sep 1, 2015·Methods : a Companion to Methods in Enzymology·Juli Rodriguez BagóShawn D Hingtgen
Mar 30, 2013·Trends in Molecular Medicine·M Sarah S BovenbergBakhos A Tannous
Apr 8, 2020·Biomaterials Science·He DongRan Mo
Aug 8, 2020·International Journal of Molecular Sciences·Manikandan MuthuJae-Wook Oh
Feb 6, 2017·Science Translational Medicine·Juli R BagóShawn D Hingtgen
May 14, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andrew BuckleyShawn D Hingtgen
Feb 29, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kevin T SheetsShawn D Hingtgen

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