Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications

Hemocompatibility of cardiovascular implants represents a major clinical challenge and, to date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from human-cell-derived tissue-engineered extracellular matrices (hTEMs) demonstrated their rece...

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Main Authors: Sarah E. Motta, Polina Zaytseva, Emanuela S. Fioretta, Valentina Lintas, Christian Breymann, Simon P. Hoerstrup, Maximilian Y. Emmert
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.867877/full
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author Sarah E. Motta
Sarah E. Motta
Polina Zaytseva
Emanuela S. Fioretta
Valentina Lintas
Christian Breymann
Simon P. Hoerstrup
Simon P. Hoerstrup
Maximilian Y. Emmert
Maximilian Y. Emmert
Maximilian Y. Emmert
Maximilian Y. Emmert
author_facet Sarah E. Motta
Sarah E. Motta
Polina Zaytseva
Emanuela S. Fioretta
Valentina Lintas
Christian Breymann
Simon P. Hoerstrup
Simon P. Hoerstrup
Maximilian Y. Emmert
Maximilian Y. Emmert
Maximilian Y. Emmert
Maximilian Y. Emmert
author_sort Sarah E. Motta
collection DOAJ
description Hemocompatibility of cardiovascular implants represents a major clinical challenge and, to date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from human-cell-derived tissue-engineered extracellular matrices (hTEMs) demonstrated their recellularization capacity in vivo and may represent promising candidates to avoid antithrombotic therapy. To further enhance their hemocompatibility, we tested hTEMs pre-endothelialization potential using human-blood-derived endothelial-colony-forming cells (ECFCs) and umbilical vein cells (control), cultured under static and dynamic orbital conditions, with either FBS or hPL. ECFCs performance was assessed via scratch assay, thereby recapitulating the surface damages occurring in transcatheter valves during crimping procedures. Our study demonstrated: feasibility to form a confluent and functional endothelium on hTEMs with expression of endothelium-specific markers; ECFCs migration and confluency restoration after crimping tests; hPL-induced formation of neo-microvessel-like structures; feasibility to pre-endothelialize hTEMs-based TEHVs and ECFCs retention on their surface after crimping. Our findings may stimulate new avenues towards next-generation pre-endothelialized implants with enhanced hemocompatibility, being beneficial for selected high-risk patients.
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spelling doaj.art-bb371a46890042029971b368d4c98ce52022-12-22T03:13:35ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-03-011010.3389/fbioe.2022.867877867877Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves ApplicationsSarah E. Motta0Sarah E. Motta1Polina Zaytseva2Emanuela S. Fioretta3Valentina Lintas4Christian Breymann5Simon P. Hoerstrup6Simon P. Hoerstrup7Maximilian Y. Emmert8Maximilian Y. Emmert9Maximilian Y. Emmert10Maximilian Y. Emmert11Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, SwitzerlandWyss Translational Center Zurich, University and ETH Zurich, Zurich, SwitzerlandInstitute for Regenerative Medicine (IREM), University of Zurich, Zurich, SwitzerlandInstitute for Regenerative Medicine (IREM), University of Zurich, Zurich, SwitzerlandInstitute for Regenerative Medicine (IREM), University of Zurich, Zurich, SwitzerlandDepartment of Obstetrics and Gynaecology, University Hospital Zurich, Obstetric Research, Feto- Maternal Haematology Research Group, Zurich, SwitzerlandInstitute for Regenerative Medicine (IREM), University of Zurich, Zurich, SwitzerlandWyss Translational Center Zurich, University and ETH Zurich, Zurich, SwitzerlandInstitute for Regenerative Medicine (IREM), University of Zurich, Zurich, SwitzerlandWyss Translational Center Zurich, University and ETH Zurich, Zurich, SwitzerlandDepartment of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, GermanyDepartment of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, GermanyHemocompatibility of cardiovascular implants represents a major clinical challenge and, to date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from human-cell-derived tissue-engineered extracellular matrices (hTEMs) demonstrated their recellularization capacity in vivo and may represent promising candidates to avoid antithrombotic therapy. To further enhance their hemocompatibility, we tested hTEMs pre-endothelialization potential using human-blood-derived endothelial-colony-forming cells (ECFCs) and umbilical vein cells (control), cultured under static and dynamic orbital conditions, with either FBS or hPL. ECFCs performance was assessed via scratch assay, thereby recapitulating the surface damages occurring in transcatheter valves during crimping procedures. Our study demonstrated: feasibility to form a confluent and functional endothelium on hTEMs with expression of endothelium-specific markers; ECFCs migration and confluency restoration after crimping tests; hPL-induced formation of neo-microvessel-like structures; feasibility to pre-endothelialize hTEMs-based TEHVs and ECFCs retention on their surface after crimping. Our findings may stimulate new avenues towards next-generation pre-endothelialized implants with enhanced hemocompatibility, being beneficial for selected high-risk patients.https://www.frontiersin.org/articles/10.3389/fbioe.2022.867877/fullhuman cell-derived tissue-engineered matricesendothelial colony forming cellanti-coagulationhemocomaptibilityscratch assayHPL
spellingShingle Sarah E. Motta
Sarah E. Motta
Polina Zaytseva
Emanuela S. Fioretta
Valentina Lintas
Christian Breymann
Simon P. Hoerstrup
Simon P. Hoerstrup
Maximilian Y. Emmert
Maximilian Y. Emmert
Maximilian Y. Emmert
Maximilian Y. Emmert
Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications
Frontiers in Bioengineering and Biotechnology
human cell-derived tissue-engineered matrices
endothelial colony forming cell
anti-coagulation
hemocomaptibility
scratch assay
HPL
title Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications
title_full Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications
title_fullStr Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications
title_full_unstemmed Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications
title_short Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications
title_sort endothelial progenitor cell based in vitro pre endothelialization of human cell derived biomimetic regenerative matrices for next generation transcatheter heart valves applications
topic human cell-derived tissue-engineered matrices
endothelial colony forming cell
anti-coagulation
hemocomaptibility
scratch assay
HPL
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.867877/full
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