title: Controlling and monitoring stem cell safety in vivo in an experimental rodent model.
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 mOct4(-) 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.
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Belgium; Molecular Small Animal Imaging Center, KU Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Leten
authors.forename: Valerie D
authors.initials: VD
authors.lastname: Roobrouck
authors.forename: Tom
authors.initials: T
authors.lastname: Struys
authors.forename: Terry C
authors.initials: TC
authors.lastname: Burns
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.forename: G
authors.initials: G
authors.lastname: Vande Velde
authors.forename: Jeanine
authors.initials: J
authors.lastname: Santermans
authors.forename: Antonio
authors.initials: A
authors.lastname: Lo Nigro
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Ibrahimi
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
authors.forename: Kristel
authors.initials: K
authors.lastname: Eggermont
authors.forename: Ivo
authors.initials: I
authors.lastname: Lambrichts
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D015774:Ganciclovir / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D049409:Luciferases, Firefly / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D023421:Models, Animal; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013234:Stem Cells / Q000166:cytology*
chemical_list: D050814:Octamer Transcription Factor-3; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D049409:Luciferases, Firefly; D015774:Ganciclovir
keywords: Adult stem cells; Gene expression; In vivo optical imaging; Magnetic resonance imaging; Syngeneic engraftment