Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model

Emerson C. Perin; Mei Tian; Frank C. Marini; Guilherme V. Silva; Yi Zheng; Fred Baimbridge; Xin Quan; Marlos R. Fernandes; Amir Gahremanpour; Daniel Young; Vincenzo Paolillo; Uday Mukhopadhyay; Agatha T. Borne; Rajesh Uthamanthil; David Brammer; James Jackson; William K. Decker; Amer M. Najjar; Michael W. Thomas; Andrei Volgin; Brian Rabinovich; Suren Soghomonyan; Hwan Jeong Jeong; Jesse M. Rios; David Steiner; Simon Robinson; Osama Mawlawi; Tinsu Pan; Jason Stafford; Vikas Kundra; Chun Li; Mian M. Alauddin; James T. Willerson; Elizabeth Shpall; Juri G. Gelovani

doi:10.1371/journal.pone.0022949

Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model

Emerson C. Perin, Mei Tian, Frank C. Marini, Guilherme V. Silva, Yi Zheng, Fred Baimbridge, Xin Quan, Marlos R. Fernandes, Amir Gahremanpour, Daniel Young, Vincenzo Paolillo, Uday Mukhopadhyay, Agatha T. Borne, Rajesh Uthamanthil, David Brammer, James Jackson, William K. Decker, Amer M. Najjar, Michael W. Thomas, Andrei VolginBrian Rabinovich, Suren Soghomonyan, Hwan Jeong Jeong, Jesse M. Rios, David Steiner, Simon Robinson, Osama Mawlawi, Tinsu Pan, Jason Stafford, Vikas Kundra, Chun Li, Mian M. Alauddin, James T. Willerson, Elizabeth Shpall, Juri G. Gelovani

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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.

Original language	English (US)
Article number	e22949
Journal	PloS one
Volume	6
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0022949
State	Published - Sep 1 2011

ASJC Scopus subject areas

General

Access to Document

10.1371/journal.pone.0022949

Cite this

Perin, E. C., Tian, M., Marini, F. C., Silva, G. V., Zheng, Y., Baimbridge, F., Quan, X., Fernandes, M. R., Gahremanpour, A., Young, D., Paolillo, V., Mukhopadhyay, U., Borne, A. T., Uthamanthil, R., Brammer, D., Jackson, J., Decker, W. K., Najjar, A. M., Thomas, M. W., ... Gelovani, J. G. (2011). Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model. PloS one, 6(9), Article e22949. https://doi.org/10.1371/journal.pone.0022949

Perin, EC, Tian, M, Marini, FC, Silva, GV, Zheng, Y, Baimbridge, F, Quan, X, Fernandes, MR, Gahremanpour, A, Young, D, Paolillo, V, Mukhopadhyay, U, Borne, AT, Uthamanthil, R, Brammer, D, Jackson, J, Decker, WK, Najjar, AM, Thomas, MW, Volgin, A, Rabinovich, B, Soghomonyan, S, Jeong, HJ, Rios, JM, Steiner, D, Robinson, S, Mawlawi, O , Pan, T , Stafford, J, Kundra, V, Li, C, Alauddin, MM, Willerson, JT, Shpall, E & Gelovani, JG 2011, 'Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model', PloS one, vol. 6, no. 9, e22949. https://doi.org/10.1371/journal.pone.0022949

@article{edd10553cc8149a9a349b82cc2076d2a,

title = "Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model",

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.",

author = "Perin, {Emerson C.} and Mei Tian and Marini, {Frank C.} and Silva, {Guilherme V.} and Yi Zheng and Fred Baimbridge and Xin Quan and Fernandes, {Marlos R.} and Amir Gahremanpour and Daniel Young and Vincenzo Paolillo and Uday Mukhopadhyay and Borne, {Agatha T.} and Rajesh Uthamanthil and David Brammer and James Jackson and Decker, {William K.} and Najjar, {Amer M.} and Thomas, {Michael W.} and Andrei Volgin and Brian Rabinovich and Suren Soghomonyan and Jeong, {Hwan Jeong} and Rios, {Jesse M.} and David Steiner and Simon Robinson and Osama Mawlawi and Tinsu Pan and Jason Stafford and Vikas Kundra and Chun Li and Alauddin, {Mian M.} and Willerson, {James T.} and Elizabeth Shpall and Gelovani, {Juri G.}",

note = "Funding Information: The authors have the following competing interest: The study was partly funded by Cordis Corporation. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. ",

year = "2011",

month = sep,

day = "1",

doi = "10.1371/journal.pone.0022949",

language = "English (US)",

volume = "6",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

TY - JOUR

T1 - Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model

AU - Perin, Emerson C.

AU - Tian, Mei

AU - Marini, Frank C.

AU - Silva, Guilherme V.

AU - Zheng, Yi

AU - Baimbridge, Fred

AU - Quan, Xin

AU - Fernandes, Marlos R.

AU - Gahremanpour, Amir

AU - Young, Daniel

AU - Paolillo, Vincenzo

AU - Mukhopadhyay, Uday

AU - Borne, Agatha T.

AU - Uthamanthil, Rajesh

AU - Brammer, David

AU - Jackson, James

AU - Decker, William K.

AU - Najjar, Amer M.

AU - Thomas, Michael W.

AU - Volgin, Andrei

AU - Rabinovich, Brian

AU - Soghomonyan, Suren

AU - Jeong, Hwan Jeong

AU - Rios, Jesse M.

AU - Steiner, David

AU - Robinson, Simon

AU - Mawlawi, Osama

AU - Pan, Tinsu

AU - Stafford, Jason

AU - Kundra, Vikas

AU - Li, Chun

AU - Alauddin, Mian M.

AU - Willerson, James T.

AU - Shpall, Elizabeth

AU - Gelovani, Juri G.

N1 - Funding Information: The authors have the following competing interest: The study was partly funded by Cordis Corporation. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052344467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052344467&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0022949

DO - 10.1371/journal.pone.0022949

M3 - Article

C2 - 21912635

AN - SCOPUS:80052344467

SN - 1932-6203

VL - 6

JO - PloS one

JF - PloS one

IS - 9

M1 - e22949

ER -

Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this