Controlling and monitoring stem cell safety in vivo in an experimental rodent model

Cindy Leten, Valerie D. Roobrouck, Tom Struys, Terence Burns, Tom Dresselaers, G. Vande Velde, Jeanine Santermans, Antonio Lo Nigro, Abdelilah Ibrahimi, Rik Gijsbers, Kristel Eggermont, Ivo Lambrichts, Catherine M. Verfaillie, Uwe Himmelreich

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2833-2844
Number of pages12
JournalStem Cells
Volume32
Issue number11
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Rodentia
Theoretical Models
Stem Cells
Bone Marrow
Safety
Suicide
Magnetic Resonance Imaging
Brain
Multimodal Imaging
Endodermal Sinus Tumor
Firefly Luciferases
Gene Expression
Germ Layers
Pluripotent Stem Cells
Ganciclovir
Adult Stem Cells
Neoplastic Stem Cells
Thymidine Kinase
Simplexvirus
Blood-Brain Barrier

Keywords

  • Adult stem cells
  • Gene expression
  • In vivo optical imaging
  • Magnetic resonance imaging
  • Syngeneic engraftment

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine
  • Medicine(all)

Cite this

Leten, C., Roobrouck, V. D., Struys, T., Burns, T., Dresselaers, T., Vande Velde, G., ... Himmelreich, U. (2014). Controlling and monitoring stem cell safety in vivo in an experimental rodent model. Stem Cells, 32(11), 2833-2844. https://doi.org/10.1002/stem.1819

Controlling and monitoring stem cell safety in vivo in an experimental rodent model. / Leten, Cindy; Roobrouck, Valerie D.; Struys, Tom; Burns, Terence; Dresselaers, Tom; Vande Velde, G.; Santermans, Jeanine; Nigro, Antonio Lo; Ibrahimi, Abdelilah; Gijsbers, Rik; Eggermont, Kristel; Lambrichts, Ivo; Verfaillie, Catherine M.; Himmelreich, Uwe.

In: Stem Cells, Vol. 32, No. 11, 01.01.2014, p. 2833-2844.

Research output: Contribution to journalArticle

Leten, C, Roobrouck, VD, Struys, T, Burns, T, Dresselaers, T, Vande Velde, G, Santermans, J, Nigro, AL, Ibrahimi, A, Gijsbers, R, Eggermont, K, Lambrichts, I, Verfaillie, CM & Himmelreich, U 2014, 'Controlling and monitoring stem cell safety in vivo in an experimental rodent model', Stem Cells, vol. 32, no. 11, pp. 2833-2844. https://doi.org/10.1002/stem.1819
Leten C, Roobrouck VD, Struys T, Burns T, Dresselaers T, Vande Velde G et al. Controlling and monitoring stem cell safety in vivo in an experimental rodent model. Stem Cells. 2014 Jan 1;32(11):2833-2844. https://doi.org/10.1002/stem.1819
Leten, Cindy ; Roobrouck, Valerie D. ; Struys, Tom ; Burns, Terence ; Dresselaers, Tom ; Vande Velde, G. ; Santermans, Jeanine ; Nigro, Antonio Lo ; Ibrahimi, Abdelilah ; Gijsbers, Rik ; Eggermont, Kristel ; Lambrichts, Ivo ; Verfaillie, Catherine M. ; Himmelreich, Uwe. / Controlling and monitoring stem cell safety in vivo in an experimental rodent model. In: Stem Cells. 2014 ; Vol. 32, No. 11. pp. 2833-2844.
@article{8d2b16d15e1543ac84d820a07678a4d7,
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.",
keywords = "Adult stem cells, Gene expression, In vivo optical imaging, Magnetic resonance imaging, Syngeneic engraftment",
author = "Cindy Leten and Roobrouck, {Valerie D.} and Tom Struys and Terence Burns and Tom Dresselaers and {Vande Velde}, G. and Jeanine Santermans and Nigro, {Antonio Lo} and Abdelilah Ibrahimi and Rik Gijsbers and Kristel Eggermont and Ivo Lambrichts and Verfaillie, {Catherine M.} and Uwe Himmelreich",
year = "2014",
month = "1",
day = "1",
doi = "10.1002/stem.1819",
language = "English (US)",
volume = "32",
pages = "2833--2844",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Controlling and monitoring stem cell safety in vivo in an experimental rodent model

AU - Leten, Cindy

AU - Roobrouck, Valerie D.

AU - Struys, Tom

AU - Burns, Terence

AU - Dresselaers, Tom

AU - Vande Velde, G.

AU - Santermans, Jeanine

AU - Nigro, Antonio Lo

AU - Ibrahimi, Abdelilah

AU - Gijsbers, Rik

AU - Eggermont, Kristel

AU - Lambrichts, Ivo

AU - Verfaillie, Catherine M.

AU - Himmelreich, Uwe

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Adult stem cells

KW - Gene expression

KW - In vivo optical imaging

KW - Magnetic resonance imaging

KW - Syngeneic engraftment

UR - http://www.scopus.com/inward/record.url?scp=84907905139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907905139&partnerID=8YFLogxK

U2 - 10.1002/stem.1819

DO - 10.1002/stem.1819

M3 - Article

C2 - 25142614

AN - SCOPUS:84907905139

VL - 32

SP - 2833

EP - 2844

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 11

ER -