Generation of vascular chimerism within donor organs

Abstract Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains chall...

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Autores principales:	Shahar Cohen, Shirly Partouche, Michael Gurevich, Vladimir Tennak, Vadym Mezhybovsky, Dmitry Azarov, Sarit Soffer-Hirschberg, Benny Hovav, Hagit Niv-Drori, Chana Weiss, Adi Borovich, Guy Cohen, Avital Wertheimer, Golan Shukrun, Moshe Israeli, Vered Yahalom, Dorit Leshem-Lev, Leor Perl, Ran Kornowski, Arnon Wiznitzer, Ana Tobar, Meora Feinmesser, Eytan Mor, Eli Atar, Eviatar Nesher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/33a32b0008404763a9672748e6e5d2e5
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spelling	oai:doaj.org-article:33a32b0008404763a9672748e6e5d2e52021-12-02T16:32:02ZGeneration of vascular chimerism within donor organs10.1038/s41598-021-92823-72045-2322https://doaj.org/article/33a32b0008404763a9672748e6e5d2e52021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92823-7https://doaj.org/toc/2045-2322Abstract Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.Shahar CohenShirly PartoucheMichael GurevichVladimir TennakVadym MezhybovskyDmitry AzarovSarit Soffer-HirschbergBenny HovavHagit Niv-DroriChana WeissAdi BorovichGuy CohenAvital WertheimerGolan ShukrunMoshe IsraeliVered YahalomDorit Leshem-LevLeor PerlRan KornowskiArnon WiznitzerAna TobarMeora FeinmesserEytan MorEli AtarEviatar NesherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shahar Cohen Shirly Partouche Michael Gurevich Vladimir Tennak Vadym Mezhybovsky Dmitry Azarov Sarit Soffer-Hirschberg Benny Hovav Hagit Niv-Drori Chana Weiss Adi Borovich Guy Cohen Avital Wertheimer Golan Shukrun Moshe Israeli Vered Yahalom Dorit Leshem-Lev Leor Perl Ran Kornowski Arnon Wiznitzer Ana Tobar Meora Feinmesser Eytan Mor Eli Atar Eviatar Nesher Generation of vascular chimerism within donor organs
description	Abstract Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.
format	article
author	Shahar Cohen Shirly Partouche Michael Gurevich Vladimir Tennak Vadym Mezhybovsky Dmitry Azarov Sarit Soffer-Hirschberg Benny Hovav Hagit Niv-Drori Chana Weiss Adi Borovich Guy Cohen Avital Wertheimer Golan Shukrun Moshe Israeli Vered Yahalom Dorit Leshem-Lev Leor Perl Ran Kornowski Arnon Wiznitzer Ana Tobar Meora Feinmesser Eytan Mor Eli Atar Eviatar Nesher
author_facet	Shahar Cohen Shirly Partouche Michael Gurevich Vladimir Tennak Vadym Mezhybovsky Dmitry Azarov Sarit Soffer-Hirschberg Benny Hovav Hagit Niv-Drori Chana Weiss Adi Borovich Guy Cohen Avital Wertheimer Golan Shukrun Moshe Israeli Vered Yahalom Dorit Leshem-Lev Leor Perl Ran Kornowski Arnon Wiznitzer Ana Tobar Meora Feinmesser Eytan Mor Eli Atar Eviatar Nesher
author_sort	Shahar Cohen
title	Generation of vascular chimerism within donor organs
title_short	Generation of vascular chimerism within donor organs
title_full	Generation of vascular chimerism within donor organs
title_fullStr	Generation of vascular chimerism within donor organs
title_full_unstemmed	Generation of vascular chimerism within donor organs
title_sort	generation of vascular chimerism within donor organs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/33a32b0008404763a9672748e6e5d2e5
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Generation of vascular chimerism within donor organs

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