Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.

<h4>Background</h4>Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numb...

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Autores principales:	Anabel S de la Garza-Rodea, Marieke C Verweij, Hester Boersma, Ietje van der Velde-van Dijke, Antoine A F de Vries, Rob C Hoeben, Dirk W van Bekkum, Emmanuel J H J Wiertz, Shoshan Knaän-Shanzer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ec215d4b23146efaeecfc7cbb4fdc57
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spelling	oai:doaj.org-article:1ec215d4b23146efaeecfc7cbb4fdc572021-11-18T07:00:44ZExploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.1932-620310.1371/journal.pone.0014493https://doaj.org/article/1ec215d4b23146efaeecfc7cbb4fdc572011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21253016/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected.<h4>Methodology/principal findings</h4>We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation.<h4>Conclusions/significance</h4>Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.Anabel S de la Garza-RodeaMarieke C VerweijHester BoersmaIetje van der Velde-van DijkeAntoine A F de VriesRob C HoebenDirk W van BekkumEmmanuel J H J WiertzShoshan Knaän-ShanzerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14493 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anabel S de la Garza-Rodea Marieke C Verweij Hester Boersma Ietje van der Velde-van Dijke Antoine A F de Vries Rob C Hoeben Dirk W van Bekkum Emmanuel J H J Wiertz Shoshan Knaän-Shanzer Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
description	<h4>Background</h4>Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected.<h4>Methodology/principal findings</h4>We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation.<h4>Conclusions/significance</h4>Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.
format	article
author	Anabel S de la Garza-Rodea Marieke C Verweij Hester Boersma Ietje van der Velde-van Dijke Antoine A F de Vries Rob C Hoeben Dirk W van Bekkum Emmanuel J H J Wiertz Shoshan Knaän-Shanzer
author_facet	Anabel S de la Garza-Rodea Marieke C Verweij Hester Boersma Ietje van der Velde-van Dijke Antoine A F de Vries Rob C Hoeben Dirk W van Bekkum Emmanuel J H J Wiertz Shoshan Knaän-Shanzer
author_sort	Anabel S de la Garza-Rodea
title	Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
title_short	Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
title_full	Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
title_fullStr	Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
title_full_unstemmed	Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
title_sort	exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1ec215d4b23146efaeecfc7cbb4fdc57
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Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.

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