CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000700629 |
Resumo: | Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptor CTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering. |
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Brazilian Journal of Medical and Biological Research |
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CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activationCTLA4Mesenchymal stem cellsImmunomodulatoryBone tissue engineeringAllogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptor CTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.Associação Brasileira de Divulgação Científica2015-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000700629Brazilian Journal of Medical and Biological Research v.48 n.7 2015reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/1414-431x20154209info:eu-repo/semantics/openAccessDai,F.Zhang,F.Sun,D.Zhang,Z.H.Dong,S.W.Xu,J.Z.eng2019-03-18T00:00:00Zoai:scielo:S0100-879X2015000700629Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2019-03-18T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
title |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
spellingShingle |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation Dai,F. CTLA4 Mesenchymal stem cells Immunomodulatory Bone tissue engineering |
title_short |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
title_full |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
title_fullStr |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
title_full_unstemmed |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
title_sort |
CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation |
author |
Dai,F. |
author_facet |
Dai,F. Zhang,F. Sun,D. Zhang,Z.H. Dong,S.W. Xu,J.Z. |
author_role |
author |
author2 |
Zhang,F. Sun,D. Zhang,Z.H. Dong,S.W. Xu,J.Z. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Dai,F. Zhang,F. Sun,D. Zhang,Z.H. Dong,S.W. Xu,J.Z. |
dc.subject.por.fl_str_mv |
CTLA4 Mesenchymal stem cells Immunomodulatory Bone tissue engineering |
topic |
CTLA4 Mesenchymal stem cells Immunomodulatory Bone tissue engineering |
description |
Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptor CTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-07-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000700629 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000700629 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1414-431x20154209 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.48 n.7 2015 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
_version_ |
1754302944568672256 |