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Title: Controlling and Monitoring Stem Cell Safety In Vivo in an Experimental Rodent Model
Authors: Leten, Cindy
Roobrouck, Valerie D.
Burns, Terry C.
Dresselaers, Tom
Vande Velde, G.
Lo Nigro, Antonio
Ibrahimi, Abdelilah
Gijsbers, Rik
Eggermont, Kristel
Verfaillie, Catherine M.
Himmelreich, Uwe
Issue Date: 2014
Source: STEM CELLS, 32 (11), p. 2833-2844
Abstract: Adult stem cells have been investigated increasingly over the past years for multiple applications. Although they have a more favorable safety profile compared to pluripotent stem cells, they are still capable of self-renewal and differentiate into several cell types. We investigated the behavior of Oct4-positive (Oct4(+)) and Oct4-negative (Oct4(-)) murine or rat bone marrow (BM)-derived stem cells in the healthy brain of syngeneic mice and rats. Engraftment of mouse and rat Oct4-positive BM-derived hypoblast-like stem cells (m/rOct4(+) BM-HypoSCs) resulted in yolk-sac tumor formation in the healthy brain which was monitored longitudinally using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). Contrast enhanced MRI confirmed the disruption of the blood brain barrier. In contrast, m/r Oct4-negative BM-derived multipotent adult progenitor cells (m/rOct4(-) BM-MAPCs) did not result in mass formation after engraftment into the brain. mOct4(+) BM-HypoSCs and mOct(-) BM-MAPCs were transduced to express enhanced green fluorescent protein, firefly luciferase (fLuc), and herpes simplex virus-thymidine kinase to follow up suicide gene expression as a potential "safety switch" for tumor-forming stem cells by multimodal imaging. Both cell lines were eradicated efficiently in vivo by ganciclovir administration indicating successful suicide gene expression in vivo, as assessed by MRI, BLI, and histology. The use of suicide genes to prevent tumor formation is in particular of interest for therapeutic approaches where stem cells are used as vehicles to deliver therapeutic genes.
Notes: [Leten, Cindy; Struys, Tom; Dresselaers, Tom; Vande Velde, G.; Himmelreich, Uwe] Katholieke Univ Leuven, Biomed MRI, Dept Imaging & Pathol, B-3000 Leuven, Belgium. [Leten, Cindy; Dresselaers, Tom; Vande Velde, G.; Himmelreich, Uwe] Katholieke Univ Leuven, Mol Small Anim Imaging Ctr, B-3000 Leuven, Belgium. [Roobrouck, Valerie D.; Lo Nigro, Antonio; Eggermont, Kristel; Verfaillie, Catherine M.] Katholieke Univ Leuven, Stem Cell Inst Leuven, Dept Dev & Regenerat, B-3000 Leuven, Belgium. [Struys, Tom; Santermans, Jeanine; Lambrichts, Ivo] Univ Hasselt, Histol Lab, Biomed Res Inst, Diepenbeek, Belgium. [Burns, Terry C.] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Ibrahimi, Abdelilah; Gijsbers, Rik] Katholieke Univ Leuven, Lab Mol Virol & Gene Therapy, B-3000 Leuven, Belgium. [Ibrahimi, Abdelilah; Gijsbers, Rik] Katholieke Univ Leuven, Leuven Viral Vector Core, B-3000 Leuven, Belgium.
Keywords: adult stem cells; gene expression; in vivo optical imaging; magnetic resonance imaging; syngeneic engraftment;Adult stem cells; Gene expression; In vivo optical imaging; Magnetic resonance imaging; Syngeneic engraftment
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ISSN: 1066-5099
e-ISSN: 1549-4918
DOI: 10.1002/stem.1819
ISI #: 000343314400004
Rights: © 2014 AlphaMed Press.
Category: A1
Type: Journal Contribution
Validations: ecoom 2015
Appears in Collections:Research publications

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