MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting

Abstract After myocardial infarction (MI), epicardial cells reactivate their embryonic program, proliferate and migrate into the damaged tissue to differentiate into fibroblasts, endothelial cells and, if adequately stimulated, to cardiomyocytes. Targeting epicardium-derived stromal cells (EpiSC) by...

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Autores principales:	Tamara Straub, Julia Nave, Pascal Bouvain, Mohammad Akbarzadeh, Siva Sai Krishna Dasa, Julia Kistner, Zhaoping Ding, Aseel Marzoq, Stefanie Stepanow, Katrin Becker, Julia Hesse, Karl Köhrer, Ulrich Flögel, Mohammad R. Ahmadian, Brent A. French, Jürgen Schrader, Sebastian Temme
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/926c75b0bc764b2880ee83245f14ba59
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spelling	oai:doaj.org-article:926c75b0bc764b2880ee83245f14ba592021-12-02T16:18:03ZMRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting10.1038/s41598-020-78600-y2045-2322https://doaj.org/article/926c75b0bc764b2880ee83245f14ba592020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78600-yhttps://doaj.org/toc/2045-2322Abstract After myocardial infarction (MI), epicardial cells reactivate their embryonic program, proliferate and migrate into the damaged tissue to differentiate into fibroblasts, endothelial cells and, if adequately stimulated, to cardiomyocytes. Targeting epicardium-derived stromal cells (EpiSC) by specific ligands might enable the direct imaging of EpiSCs after MI to better understand their biology, but also may permit the cell-specific delivery of small molecules to improve the post-MI healing process. Therefore, the aim of this study was to identify specific peptides by phage display screening to enable EpiSC specific cargo delivery by active targeting. To this end, we utilized a sequential panning of a phage library on cultured rat EpiSCs and then subtracted phage that nonspecifically bound blood immune cells. EpiSC specific phage were analyzed by deep sequencing and bioinformatics analysis to identify a total of 78 300 ± 31 900 different, EpiSC-specific, peptide insertion sequences. Flow cytometry of the five most highly abundant peptides (EP1, -2, –3, -7 or EP9) showed strong binding to EpiSCs but not to blood immune cells. The best binding properties were found for EP9 which was further studied by surface plasmon resonance (SPR). SPR revealed rapid and stable association of EpiSCs with EP9. As a negative control, THP-1 monocytes did not associate with EP9. Coupling of EP9 to perfluorocarbon nanoemulsions (PFCs) resulted in the efficient delivery of 19F cargo to EpiSCs and enabled their visualization by 19F MRI. Moreover, active targeting of EpiSCs by EP9-labelled PFCs was able to outcompete the strong phagocytic uptake of PFCs by circulating monocytes. In summary, we have identified a 7-mer peptide, (EP9) that binds to EpiSCs with high affinity and specificity. This peptide can be used to deliver small molecule cargos such as contrast agents to permit future in vivo tracking of EpiSCs by molecular imaging and to transfer small pharmaceutical molecules to modulate the biological activity of EpiSCs.Tamara StraubJulia NavePascal BouvainMohammad AkbarzadehSiva Sai Krishna DasaJulia KistnerZhaoping DingAseel MarzoqStefanie StepanowKatrin BeckerJulia HesseKarl KöhrerUlrich FlögelMohammad R. AhmadianBrent A. FrenchJürgen SchraderSebastian TemmeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tamara Straub Julia Nave Pascal Bouvain Mohammad Akbarzadeh Siva Sai Krishna Dasa Julia Kistner Zhaoping Ding Aseel Marzoq Stefanie Stepanow Katrin Becker Julia Hesse Karl Köhrer Ulrich Flögel Mohammad R. Ahmadian Brent A. French Jürgen Schrader Sebastian Temme MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
description	Abstract After myocardial infarction (MI), epicardial cells reactivate their embryonic program, proliferate and migrate into the damaged tissue to differentiate into fibroblasts, endothelial cells and, if adequately stimulated, to cardiomyocytes. Targeting epicardium-derived stromal cells (EpiSC) by specific ligands might enable the direct imaging of EpiSCs after MI to better understand their biology, but also may permit the cell-specific delivery of small molecules to improve the post-MI healing process. Therefore, the aim of this study was to identify specific peptides by phage display screening to enable EpiSC specific cargo delivery by active targeting. To this end, we utilized a sequential panning of a phage library on cultured rat EpiSCs and then subtracted phage that nonspecifically bound blood immune cells. EpiSC specific phage were analyzed by deep sequencing and bioinformatics analysis to identify a total of 78 300 ± 31 900 different, EpiSC-specific, peptide insertion sequences. Flow cytometry of the five most highly abundant peptides (EP1, -2, –3, -7 or EP9) showed strong binding to EpiSCs but not to blood immune cells. The best binding properties were found for EP9 which was further studied by surface plasmon resonance (SPR). SPR revealed rapid and stable association of EpiSCs with EP9. As a negative control, THP-1 monocytes did not associate with EP9. Coupling of EP9 to perfluorocarbon nanoemulsions (PFCs) resulted in the efficient delivery of 19F cargo to EpiSCs and enabled their visualization by 19F MRI. Moreover, active targeting of EpiSCs by EP9-labelled PFCs was able to outcompete the strong phagocytic uptake of PFCs by circulating monocytes. In summary, we have identified a 7-mer peptide, (EP9) that binds to EpiSCs with high affinity and specificity. This peptide can be used to deliver small molecule cargos such as contrast agents to permit future in vivo tracking of EpiSCs by molecular imaging and to transfer small pharmaceutical molecules to modulate the biological activity of EpiSCs.
format	article
author	Tamara Straub Julia Nave Pascal Bouvain Mohammad Akbarzadeh Siva Sai Krishna Dasa Julia Kistner Zhaoping Ding Aseel Marzoq Stefanie Stepanow Katrin Becker Julia Hesse Karl Köhrer Ulrich Flögel Mohammad R. Ahmadian Brent A. French Jürgen Schrader Sebastian Temme
author_facet	Tamara Straub Julia Nave Pascal Bouvain Mohammad Akbarzadeh Siva Sai Krishna Dasa Julia Kistner Zhaoping Ding Aseel Marzoq Stefanie Stepanow Katrin Becker Julia Hesse Karl Köhrer Ulrich Flögel Mohammad R. Ahmadian Brent A. French Jürgen Schrader Sebastian Temme
author_sort	Tamara Straub
title	MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
title_short	MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
title_full	MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
title_fullStr	MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
title_full_unstemmed	MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
title_sort	mri-based molecular imaging of epicardium-derived stromal cells (episc) by peptide-mediated active targeting
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/926c75b0bc764b2880ee83245f14ba59
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MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting

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