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Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Metho... Full description

Journal Title: Radiology September 2016, Vol.280(3), pp.815-25
Main Author: Parashurama, Natesh
Other Authors: Ahn, Byeong-Cheol , Ziv, Keren , Ito, Ken , Paulmurugan, Ramasamy , Willmann, Jürgen K , Chung, Jaehoon , Ikeno, Fumiaki , Swanson, Julia C , Merk, Denis R , Lyons, Jennifer K , Yerushalmi, David , Teramoto, Tomohiko , Kosuge, Hisanori , Dao, Catherine N , Ray, Pritha , Patel, Manishkumar , Chang, Ya-Fang , Mahmoudi, Morteza , Cohen, Jeff Eric , Goldstone, Andrew Brooks , Habte, Frezghi , Bhaumik, Srabani , Yaghoubi, Shahriar , Robbins, Robert C , Dash, Rajesh , Yang, Phillip C , Brinton, Todd J , Yock, Paul G , Mcconnell, Michael V , Gambhir, Sanjiv S
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1527-1315 ; PMID: 27308957 Version:1 ; DOI: 10.1148/radiol.2016140049
Link: http://pubmed.gov/27308957
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title: Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction
format: Article
creator:
  • Parashurama, Natesh
  • Ahn, Byeong-Cheol
  • Ziv, Keren
  • Ito, Ken
  • Paulmurugan, Ramasamy
  • Willmann, Jürgen K
  • Chung, Jaehoon
  • Ikeno, Fumiaki
  • Swanson, Julia C
  • Merk, Denis R
  • Lyons, Jennifer K
  • Yerushalmi, David
  • Teramoto, Tomohiko
  • Kosuge, Hisanori
  • Dao, Catherine N
  • Ray, Pritha
  • Patel, Manishkumar
  • Chang, Ya-Fang
  • Mahmoudi, Morteza
  • Cohen, Jeff Eric
  • Goldstone, Andrew Brooks
  • Habte, Frezghi
  • Bhaumik, Srabani
  • Yaghoubi, Shahriar
  • Robbins, Robert C
  • Dash, Rajesh
  • Yang, Phillip C
  • Brinton, Todd J
  • Yock, Paul G
  • Mcconnell, Michael V
  • Gambhir, Sanjiv S
subjects:
  • Genes, Reporter
  • Molecular Imaging
  • Multimodal Imaging
  • Mesenchymal Stem Cell Transplantation -- Methods
  • Myocardial Infarction -- Diagnostic Imaging
ispartof: Radiology, September 2016, Vol.280(3), pp.815-25
description: Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.
language: eng
source:
identifier: E-ISSN: 1527-1315 ; PMID: 27308957 Version:1 ; DOI: 10.1148/radiol.2016140049
fulltext: no_fulltext
issn:
  • 15271315
  • 1527-1315
url: Link


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titleMultimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction
creatorParashurama, Natesh ; Ahn, Byeong-Cheol ; Ziv, Keren ; Ito, Ken ; Paulmurugan, Ramasamy ; Willmann, Jürgen K ; Chung, Jaehoon ; Ikeno, Fumiaki ; Swanson, Julia C ; Merk, Denis R ; Lyons, Jennifer K ; Yerushalmi, David ; Teramoto, Tomohiko ; Kosuge, Hisanori ; Dao, Catherine N ; Ray, Pritha ; Patel, Manishkumar ; Chang, Ya-Fang ; Mahmoudi, Morteza ; Cohen, Jeff Eric ; Goldstone, Andrew Brooks ; Habte, Frezghi ; Bhaumik, Srabani ; Yaghoubi, Shahriar ; Robbins, Robert C ; Dash, Rajesh ; Yang, Phillip C ; Brinton, Todd J ; Yock, Paul G ; Mcconnell, Michael V ; Gambhir, Sanjiv S
ispartofRadiology, September 2016, Vol.280(3), pp.815-25
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subjectGenes, Reporter ; Molecular Imaging ; Multimodal Imaging ; Mesenchymal Stem Cell Transplantation -- Methods ; Myocardial Infarction -- Diagnostic Imaging
descriptionPurpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.
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titleMultimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction
descriptionPurpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.
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titleMultimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction
authorParashurama, Natesh ; Ahn, Byeong-Cheol ; Ziv, Keren ; Ito, Ken ; Paulmurugan, Ramasamy ; Willmann, Jürgen K ; Chung, Jaehoon ; Ikeno, Fumiaki ; Swanson, Julia C ; Merk, Denis R ; Lyons, Jennifer K ; Yerushalmi, David ; Teramoto, Tomohiko ; Kosuge, Hisanori ; Dao, Catherine N ; Ray, Pritha ; Patel, Manishkumar ; Chang, Ya-Fang ; Mahmoudi, Morteza ; Cohen, Jeff Eric ; Goldstone, Andrew Brooks ; Habte, Frezghi ; Bhaumik, Srabani ; Yaghoubi, Shahriar ; Robbins, Robert C ; Dash, Rajesh ; Yang, Phillip C ; Brinton, Todd J ; Yock, Paul G ; Mcconnell, Michael V ; Gambhir, Sanjiv S
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26Yang, Phillip C
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atitleMultimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction
jtitleRadiology
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volume280
issue3
spage815
pages815-825
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abstractPurpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.
doi10.1148/radiol.2016140049
pmid27308957
issn00338419
oafree_for_read
date2016-09