Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device

Abstract Low haemocompatibility of left ventricular assist devices (LVAD) surfaces necessitates anticoagulative therapy. Endothelial cell (EC) seeding can support haemocompatibility, however, the availability of autologous ECs is limited. In contrast, allogeneic ECs are readily available in sufficie...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Constanca Figueiredo, Dorothee Eicke, Yuliia Yuzefovych, Murat Avsar, Jasmin Sarah Hanke, Michael Pflaum, Jan-Dieter Schmitto, Rainer Blasczyk, Axel Haverich, Bettina Wiegmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/843cd085bf6c4f92b6355918a87d0e9a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:843cd085bf6c4f92b6355918a87d0e9a
record_format	dspace
spelling	oai:doaj.org-article:843cd085bf6c4f92b6355918a87d0e9a2021-12-02T15:09:46ZLow immunogenic endothelial cells endothelialize the Left Ventricular Assist Device10.1038/s41598-019-47780-72045-2322https://doaj.org/article/843cd085bf6c4f92b6355918a87d0e9a2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47780-7https://doaj.org/toc/2045-2322Abstract Low haemocompatibility of left ventricular assist devices (LVAD) surfaces necessitates anticoagulative therapy. Endothelial cell (EC) seeding can support haemocompatibility, however, the availability of autologous ECs is limited. In contrast, allogeneic ECs are readily available in sufficient quantity, but HLA disparities induce harmful immune responses causing EC loss. In this study, we investigated the feasibility of using allogeneic low immunogenic ECs to endothelialize LVAD sintered inflow cannulas (SIC). To reduce the immunogenicity of ECs, we applied an inducible lentiviral vector to deliver short-hairpins RNA to silence HLA class I expression. HLA class I expression on ECs was conditionally silenced by up to 70%. Sufficient and comparable endothelialization rates were achieved with HLA-expressing or HLA-silenced ECs. Cell proliferation was not impaired by cell-to-Sintered Inflow Cannulas (SIC) contact or by silencing HLA expression. The levels of endothelial phenotypic and thrombogenic markers or cytokine secretion profiles remained unaffected. HLA-silenced ECs-coated SIC exhibited reduced thrombogenicity. In contrast to native ECs, HLA-silenced ECs showed lower cell lysis rates when exposed to allogeneic T cells or specific anti-HLA antibodies. Allogeneic HLA-silenced ECs could potentially become a valuable source for LVAD endothelialization to reduce immunogenicity and correspondingly the need for anticoagulative therapy which can entail severe side effects.Constanca FigueiredoDorothee EickeYuliia YuzefovychMurat AvsarJasmin Sarah HankeMichael PflaumJan-Dieter SchmittoRainer BlasczykAxel HaverichBettina WiegmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Constanca Figueiredo Dorothee Eicke Yuliia Yuzefovych Murat Avsar Jasmin Sarah Hanke Michael Pflaum Jan-Dieter Schmitto Rainer Blasczyk Axel Haverich Bettina Wiegmann Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
description	Abstract Low haemocompatibility of left ventricular assist devices (LVAD) surfaces necessitates anticoagulative therapy. Endothelial cell (EC) seeding can support haemocompatibility, however, the availability of autologous ECs is limited. In contrast, allogeneic ECs are readily available in sufficient quantity, but HLA disparities induce harmful immune responses causing EC loss. In this study, we investigated the feasibility of using allogeneic low immunogenic ECs to endothelialize LVAD sintered inflow cannulas (SIC). To reduce the immunogenicity of ECs, we applied an inducible lentiviral vector to deliver short-hairpins RNA to silence HLA class I expression. HLA class I expression on ECs was conditionally silenced by up to 70%. Sufficient and comparable endothelialization rates were achieved with HLA-expressing or HLA-silenced ECs. Cell proliferation was not impaired by cell-to-Sintered Inflow Cannulas (SIC) contact or by silencing HLA expression. The levels of endothelial phenotypic and thrombogenic markers or cytokine secretion profiles remained unaffected. HLA-silenced ECs-coated SIC exhibited reduced thrombogenicity. In contrast to native ECs, HLA-silenced ECs showed lower cell lysis rates when exposed to allogeneic T cells or specific anti-HLA antibodies. Allogeneic HLA-silenced ECs could potentially become a valuable source for LVAD endothelialization to reduce immunogenicity and correspondingly the need for anticoagulative therapy which can entail severe side effects.
format	article
author	Constanca Figueiredo Dorothee Eicke Yuliia Yuzefovych Murat Avsar Jasmin Sarah Hanke Michael Pflaum Jan-Dieter Schmitto Rainer Blasczyk Axel Haverich Bettina Wiegmann
author_facet	Constanca Figueiredo Dorothee Eicke Yuliia Yuzefovych Murat Avsar Jasmin Sarah Hanke Michael Pflaum Jan-Dieter Schmitto Rainer Blasczyk Axel Haverich Bettina Wiegmann
author_sort	Constanca Figueiredo
title	Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
title_short	Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
title_full	Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
title_fullStr	Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
title_full_unstemmed	Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
title_sort	low immunogenic endothelial cells endothelialize the left ventricular assist device
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/843cd085bf6c4f92b6355918a87d0e9a
work_keys_str_mv	AT constancafigueiredo lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT dorotheeeicke lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT yuliiayuzefovych lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT muratavsar lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT jasminsarahhanke lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT michaelpflaum lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT jandieterschmitto lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT rainerblasczyk lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT axelhaverich lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice AT bettinawiegmann lowimmunogenicendothelialcellsendothelializetheleftventricularassistdevice
_version_	1718387763281133568

Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device

Ejemplares similares