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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-78600-y |
| _version_ | 1818749589653553152 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:06:11Z |
| format | Article |
| id | doaj.art-926c75b0bc764b2880ee83245f14ba59 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:06:11Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-926c75b0bc764b2880ee83245f14ba592022-12-21T21:21:36ZengNature PortfolioScientific Reports2045-23222020-12-0110111410.1038/s41598-020-78600-yMRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targetingTamara Straub0Julia Nave1Pascal Bouvain2Mohammad Akbarzadeh3Siva Sai Krishna Dasa4Julia Kistner5Zhaoping Ding6Aseel Marzoq7Stefanie Stepanow8Katrin Becker9Julia Hesse10Karl Köhrer11Ulrich Flögel12Mohammad R. Ahmadian13Brent A. French14Jürgen Schrader15Sebastian Temme16Department of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Biochemistry and Molecular Biology II, Heinrich Heine University DüsseldorfRobert M. Berne Cardiovascular Research Center, University of VirginiaDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfBiological and Medical Research Center (BMFZ), Genomics and Transcriptomics Laboratory, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfBiological and Medical Research Center (BMFZ), Genomics and Transcriptomics Laboratory, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Biochemistry and Molecular Biology II, Heinrich Heine University DüsseldorfDepartment of Biomedical Engineering, University of VirginiaDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfDepartment of Molecular Cardiology, Heinrich Heine University DüsseldorfAbstract 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.https://doi.org/10.1038/s41598-020-78600-y |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-78600-y |
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