Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model
Identifieur interne : 004517 ( Pmc/Curation ); précédent : 004516; suivant : 004518Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model
Auteurs : Emerson C. Perin [États-Unis] ; Mei Tian [États-Unis] ; Frank C. Marini [États-Unis] ; Guilherme V. Silva [États-Unis] ; Yi Zheng [États-Unis] ; Fred Baimbridge [États-Unis] ; Xin Quan [États-Unis] ; Marlos R. Fernandes [États-Unis] ; Amir Gahremanpour [États-Unis] ; Daniel Young [États-Unis] ; Vincenzo Paolillo [États-Unis] ; Uday Mukhopadhyay [États-Unis] ; Agatha T. Borne [États-Unis] ; Rajesh Uthamanthil [États-Unis] ; David Brammer [États-Unis] ; James Jackson [États-Unis] ; William K. Decker [États-Unis] ; Amer M. Najjar [États-Unis] ; Michael W. Thomas [États-Unis] ; Andrei Volgin [États-Unis] ; Brian Rabinovich [États-Unis] ; Suren Soghomonyan [États-Unis] ; Hwan-Jeong Jeong [États-Unis] ; Jesse M. Rios [États-Unis] ; David Steiner [États-Unis] ; Simon Robinson [États-Unis] ; Osama Mawlawi [États-Unis] ; Tinsu Pan [États-Unis] ; Jason Stafford [États-Unis] ; Vikas Kundra [États-Unis] ; Chun Li [États-Unis] ; Mian M. Alauddin [États-Unis] ; James T. Willerson [États-Unis] ; Elizabeth Shpall [États-Unis] ; Juri G. Gelovani [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.
Url:
DOI: 10.1371/journal.pone.0022949
PubMed: 21912635
PubMed Central: 3164664
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<author><name sortKey="Silva, Guilherme V" sort="Silva, Guilherme V" uniqKey="Silva G" first="Guilherme V." last="Silva">Guilherme V. Silva</name>
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<author><name sortKey="Quan, Xin" sort="Quan, Xin" uniqKey="Quan X" first="Xin" last="Quan">Xin Quan</name>
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<author><name sortKey="Fernandes, Marlos R" sort="Fernandes, Marlos R" uniqKey="Fernandes M" first="Marlos R." last="Fernandes">Marlos R. Fernandes</name>
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<author><name sortKey="Gahremanpour, Amir" sort="Gahremanpour, Amir" uniqKey="Gahremanpour A" first="Amir" last="Gahremanpour">Amir Gahremanpour</name>
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<author><name sortKey="Young, Daniel" sort="Young, Daniel" uniqKey="Young D" first="Daniel" last="Young">Daniel Young</name>
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<author><name sortKey="Paolillo, Vincenzo" sort="Paolillo, Vincenzo" uniqKey="Paolillo V" first="Vincenzo" last="Paolillo">Vincenzo Paolillo</name>
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<author><name sortKey="Mukhopadhyay, Uday" sort="Mukhopadhyay, Uday" uniqKey="Mukhopadhyay U" first="Uday" last="Mukhopadhyay">Uday Mukhopadhyay</name>
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<author><name sortKey="Uthamanthil, Rajesh" sort="Uthamanthil, Rajesh" uniqKey="Uthamanthil R" first="Rajesh" last="Uthamanthil">Rajesh Uthamanthil</name>
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<author><name sortKey="Jackson, James" sort="Jackson, James" uniqKey="Jackson J" first="James" last="Jackson">James Jackson</name>
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<wicri:regionArea>Department of Nuclear Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
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<author><name sortKey="Decker, William K" sort="Decker, William K" uniqKey="Decker W" first="William K." last="Decker">William K. Decker</name>
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<author><name sortKey="Najjar, Amer M" sort="Najjar, Amer M" uniqKey="Najjar A" first="Amer M." last="Najjar">Amer M. Najjar</name>
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<author><name sortKey="Thomas, Michael W" sort="Thomas, Michael W" uniqKey="Thomas M" first="Michael W." last="Thomas">Michael W. Thomas</name>
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<author><name sortKey="Volgin, Andrei" sort="Volgin, Andrei" uniqKey="Volgin A" first="Andrei" last="Volgin">Andrei Volgin</name>
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<author><name sortKey="Rabinovich, Brian" sort="Rabinovich, Brian" uniqKey="Rabinovich B" first="Brian" last="Rabinovich">Brian Rabinovich</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
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<author><name sortKey="Soghomonyan, Suren" sort="Soghomonyan, Suren" uniqKey="Soghomonyan S" first="Suren" last="Soghomonyan">Suren Soghomonyan</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
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<author><name sortKey="Jeong, Hwan Jeong" sort="Jeong, Hwan Jeong" uniqKey="Jeong H" first="Hwan-Jeong" last="Jeong">Hwan-Jeong Jeong</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
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<author><name sortKey="Rios, Jesse M" sort="Rios, Jesse M" uniqKey="Rios J" first="Jesse M." last="Rios">Jesse M. Rios</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
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<author><name sortKey="Steiner, David" sort="Steiner, David" uniqKey="Steiner D" first="David" last="Steiner">David Steiner</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
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<author><name sortKey="Robinson, Simon" sort="Robinson, Simon" uniqKey="Robinson S" first="Simon" last="Robinson">Simon Robinson</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mawlawi, Osama" sort="Mawlawi, Osama" uniqKey="Mawlawi O" first="Osama" last="Mawlawi">Osama Mawlawi</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
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<author><name sortKey="Pan, Tinsu" sort="Pan, Tinsu" uniqKey="Pan T" first="Tinsu" last="Pan">Tinsu Pan</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
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<author><name sortKey="Stafford, Jason" sort="Stafford, Jason" uniqKey="Stafford J" first="Jason" last="Stafford">Jason Stafford</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kundra, Vikas" sort="Kundra, Vikas" uniqKey="Kundra V" first="Vikas" last="Kundra">Vikas Kundra</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Li, Chun" sort="Li, Chun" uniqKey="Li C" first="Chun" last="Li">Chun Li</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Alauddin, Mian M" sort="Alauddin, Mian M" uniqKey="Alauddin M" first="Mian M." last="Alauddin">Mian M. Alauddin</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
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<author><name sortKey="Willerson, James T" sort="Willerson, James T" uniqKey="Willerson J" first="James T." last="Willerson">James T. Willerson</name>
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<author><name sortKey="Shpall, Elizabeth" sort="Shpall, Elizabeth" uniqKey="Shpall E" first="Elizabeth" last="Shpall">Elizabeth Shpall</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gelovani, Juri G" sort="Gelovani, Juri G" uniqKey="Gelovani J" first="Juri G." last="Gelovani">Juri G. Gelovani</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model</title>
<author><name sortKey="Perin, Emerson C" sort="Perin, Emerson C" uniqKey="Perin E" first="Emerson C." last="Perin">Emerson C. Perin</name>
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<author><name sortKey="Tian, Mei" sort="Tian, Mei" uniqKey="Tian M" first="Mei" last="Tian">Mei Tian</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marini, Frank C" sort="Marini, Frank C" uniqKey="Marini F" first="Frank C." last="Marini">Frank C. Marini</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Silva, Guilherme V" sort="Silva, Guilherme V" uniqKey="Silva G" first="Guilherme V." last="Silva">Guilherme V. Silva</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zheng, Yi" sort="Zheng, Yi" uniqKey="Zheng Y" first="Yi" last="Zheng">Yi Zheng</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Baimbridge, Fred" sort="Baimbridge, Fred" uniqKey="Baimbridge F" first="Fred" last="Baimbridge">Fred Baimbridge</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quan, Xin" sort="Quan, Xin" uniqKey="Quan X" first="Xin" last="Quan">Xin Quan</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fernandes, Marlos R" sort="Fernandes, Marlos R" uniqKey="Fernandes M" first="Marlos R." last="Fernandes">Marlos R. Fernandes</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gahremanpour, Amir" sort="Gahremanpour, Amir" uniqKey="Gahremanpour A" first="Amir" last="Gahremanpour">Amir Gahremanpour</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Young, Daniel" sort="Young, Daniel" uniqKey="Young D" first="Daniel" last="Young">Daniel Young</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Paolillo, Vincenzo" sort="Paolillo, Vincenzo" uniqKey="Paolillo V" first="Vincenzo" last="Paolillo">Vincenzo Paolillo</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mukhopadhyay, Uday" sort="Mukhopadhyay, Uday" uniqKey="Mukhopadhyay U" first="Uday" last="Mukhopadhyay">Uday Mukhopadhyay</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Borne, Agatha T" sort="Borne, Agatha T" uniqKey="Borne A" first="Agatha T." last="Borne">Agatha T. Borne</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Uthamanthil, Rajesh" sort="Uthamanthil, Rajesh" uniqKey="Uthamanthil R" first="Rajesh" last="Uthamanthil">Rajesh Uthamanthil</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Brammer, David" sort="Brammer, David" uniqKey="Brammer D" first="David" last="Brammer">David Brammer</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jackson, James" sort="Jackson, James" uniqKey="Jackson J" first="James" last="Jackson">James Jackson</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Department of Nuclear Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Nuclear Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Decker, William K" sort="Decker, William K" uniqKey="Decker W" first="William K." last="Decker">William K. Decker</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Najjar, Amer M" sort="Najjar, Amer M" uniqKey="Najjar A" first="Amer M." last="Najjar">Amer M. Najjar</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Thomas, Michael W" sort="Thomas, Michael W" uniqKey="Thomas M" first="Michael W." last="Thomas">Michael W. Thomas</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Volgin, Andrei" sort="Volgin, Andrei" uniqKey="Volgin A" first="Andrei" last="Volgin">Andrei Volgin</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rabinovich, Brian" sort="Rabinovich, Brian" uniqKey="Rabinovich B" first="Brian" last="Rabinovich">Brian Rabinovich</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Soghomonyan, Suren" sort="Soghomonyan, Suren" uniqKey="Soghomonyan S" first="Suren" last="Soghomonyan">Suren Soghomonyan</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jeong, Hwan Jeong" sort="Jeong, Hwan Jeong" uniqKey="Jeong H" first="Hwan-Jeong" last="Jeong">Hwan-Jeong Jeong</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rios, Jesse M" sort="Rios, Jesse M" uniqKey="Rios J" first="Jesse M." last="Rios">Jesse M. Rios</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Steiner, David" sort="Steiner, David" uniqKey="Steiner D" first="David" last="Steiner">David Steiner</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Robinson, Simon" sort="Robinson, Simon" uniqKey="Robinson S" first="Simon" last="Robinson">Simon Robinson</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mawlawi, Osama" sort="Mawlawi, Osama" uniqKey="Mawlawi O" first="Osama" last="Mawlawi">Osama Mawlawi</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pan, Tinsu" sort="Pan, Tinsu" uniqKey="Pan T" first="Tinsu" last="Pan">Tinsu Pan</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stafford, Jason" sort="Stafford, Jason" uniqKey="Stafford J" first="Jason" last="Stafford">Jason Stafford</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kundra, Vikas" sort="Kundra, Vikas" uniqKey="Kundra V" first="Vikas" last="Kundra">Vikas Kundra</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Li, Chun" sort="Li, Chun" uniqKey="Li C" first="Chun" last="Li">Chun Li</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Alauddin, Mian M" sort="Alauddin, Mian M" uniqKey="Alauddin M" first="Mian M." last="Alauddin">Mian M. Alauddin</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Willerson, James T" sort="Willerson, James T" uniqKey="Willerson J" first="James T." last="Willerson">James T. Willerson</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shpall, Elizabeth" sort="Shpall, Elizabeth" uniqKey="Shpall E" first="Elizabeth" last="Shpall">Elizabeth Shpall</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gelovani, Juri G" sort="Gelovani, Juri G" uniqKey="Gelovani J" first="Juri G." last="Gelovani">Juri G. Gelovani</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [<sup>18</sup>
F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [<sup>18</sup>
F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [<sup>18</sup>
F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [<sup>18</sup>
F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21912635</article-id>
<article-id pub-id-type="pmc">3164664</article-id>
<article-id pub-id-type="publisher-id">PONE-D-11-05836</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0022949</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology</subject>
<subj-group><subject>Molecular Cell Biology</subject>
<subj-group><subject>Cellular Types</subject>
<subj-group><subject>Stem Cells</subject>
<subj-group><subject>Mesenchymal Stem Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject>
<subj-group><subject>Cardiovascular</subject>
<subj-group><subject>Myocardial Infarction</subject>
</subj-group>
</subj-group>
<subj-group><subject>Radiology</subject>
<subj-group><subject>Nuclear Medicine</subject>
<subj-group><subject>PET imaging</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model</article-title>
<alt-title alt-title-type="running-head">Long-Term Imaging of MSCs Implanted into the Heart</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Perin</surname>
<given-names>Emerson C.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Tian</surname>
<given-names>Mei</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marini</surname>
<given-names>Frank C.</given-names>
<suffix>III</suffix>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Silva</surname>
<given-names>Guilherme V.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zheng</surname>
<given-names>Yi</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baimbridge</surname>
<given-names>Fred</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Quan</surname>
<given-names>Xin</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fernandes</surname>
<given-names>Marlos R.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gahremanpour</surname>
<given-names>Amir</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Young</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Paolillo</surname>
<given-names>Vincenzo</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mukhopadhyay</surname>
<given-names>Uday</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Borne</surname>
<given-names>Agatha T.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Uthamanthil</surname>
<given-names>Rajesh</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brammer</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jackson</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
</contrib>
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<given-names>William K.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
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<given-names>Amer M.</given-names>
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<xref ref-type="aff" rid="aff2"><sup>2</sup>
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<given-names>Michael W.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
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<given-names>Andrei</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
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<given-names>Brian</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Soghomonyan</surname>
<given-names>Suren</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
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<given-names>Hwan-Jeong</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
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<given-names>Jesse M.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
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<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Robinson</surname>
<given-names>Simon</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
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<given-names>Osama</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
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<given-names>Tinsu</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stafford</surname>
<given-names>Jason</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kundra</surname>
<given-names>Vikas</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Chun</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
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<contrib contrib-type="author"><name><surname>Alauddin</surname>
<given-names>Mian M.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Willerson</surname>
<given-names>James T.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shpall</surname>
<given-names>Elizabeth</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gelovani</surname>
<given-names>Juri G.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Department of Stem Cell Transplant and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>Department of Veterinary Surgery and Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</aff>
<aff id="aff5"><label>5</label>
<addr-line>Department of Nuclear Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</aff>
<aff id="aff6"><label>6</label>
<addr-line>Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Gambhir</surname>
<given-names>Sanjiv Sam</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Stanford University Medical Center, United States of America</aff>
<author-notes><corresp id="cor1">* E-mail: <email>jgelovani@mdanderson.org</email>
</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: JGG ECP ES MT JTW. Performed the experiments: MT FB MRF AG JMR ES YZ GVS ECP MWT WKD DS MA VP UM SS H-JJ NF JJ OM CL XQ DY RU ATB DB FCM AMN AV BR. Analyzed the data: MT TP VK JS FCM DY AMN ECP AV BR JGG JTW. Contributed reagents/materials/analysis tools: MMA VP UM MWT SR WKD DS ES CL AV BR ES. Wrote the paper: JGG ECP MT FCM.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>1</day>
<month>9</month>
<year>2011</year>
</pub-date>
<volume>6</volume>
<issue>9</issue>
<elocation-id>e22949</elocation-id>
<history><date date-type="received"><day>30</day>
<month>3</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>1</day>
<month>7</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Perin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<abstract><p>The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [<sup>18</sup>
F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [<sup>18</sup>
F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [<sup>18</sup>
F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [<sup>18</sup>
F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.</p>
</abstract>
<counts><page-count count="13"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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