Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells

Federico Franchi, Karen M. Peterson, Ramasamy Paulmurugan, Clifford Folmes, Ian R Lanza, Amir Lerman, Martin G Rodriguez-Porcel

Research output: Contribution to journalArticle

Abstract

Purpose: Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells. Procedures: We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR). Results: The sensor activity showed an inverse relationship with mitochondrial function (R2 = −0.975, p = 0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1-Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry. Conclusions: Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular Imaging and Biology
DOIs
StateAccepted/In press - Feb 10 2016

Fingerprint

Mesenchymal Stromal Cells
Reporter Genes
Firefly Luciferases
Stem Cells
Myocardial Reperfusion
Reperfusion
Myocardial Ischemia
Cell Survival
Mitochondria
Ischemia
Phenotype
Sensitivity and Specificity
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells. / Franchi, Federico; Peterson, Karen M.; Paulmurugan, Ramasamy; Folmes, Clifford; Lanza, Ian R; Lerman, Amir; Rodriguez-Porcel, Martin G.

In: Molecular Imaging and Biology, 10.02.2016, p. 1-9.

Research output: Contribution to journalArticle

@article{aec3d5ef4b3848e4a62a22b0555c7194,
title = "Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells",
abstract = "Purpose: Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells. Procedures: We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR). Results: The sensor activity showed an inverse relationship with mitochondrial function (R2 = −0.975, p = 0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1-Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry. Conclusions: Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells.",
author = "Federico Franchi and Peterson, {Karen M.} and Ramasamy Paulmurugan and Clifford Folmes and Lanza, {Ian R} and Amir Lerman and Rodriguez-Porcel, {Martin G}",
year = "2016",
month = "2",
day = "10",
doi = "10.1007/s11307-016-0929-x",
language = "English (US)",
pages = "1--9",
journal = "Molecular Imaging and Biology",
issn = "1536-1632",
publisher = "Springer New York",

}

TY - JOUR

T1 - Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells

AU - Franchi, Federico

AU - Peterson, Karen M.

AU - Paulmurugan, Ramasamy

AU - Folmes, Clifford

AU - Lanza, Ian R

AU - Lerman, Amir

AU - Rodriguez-Porcel, Martin G

PY - 2016/2/10

Y1 - 2016/2/10

N2 - Purpose: Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells. Procedures: We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR). Results: The sensor activity showed an inverse relationship with mitochondrial function (R2 = −0.975, p = 0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1-Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry. Conclusions: Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells.

AB - Purpose: Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells. Procedures: We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR). Results: The sensor activity showed an inverse relationship with mitochondrial function (R2 = −0.975, p = 0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1-Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry. Conclusions: Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells.

UR - http://www.scopus.com/inward/record.url?scp=84957649165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957649165&partnerID=8YFLogxK

U2 - 10.1007/s11307-016-0929-x

DO - 10.1007/s11307-016-0929-x

M3 - Article

C2 - 26865378

AN - SCOPUS:84957649165

SP - 1

EP - 9

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

SN - 1536-1632

ER -