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CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

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Title: CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation
Authors: Dai, F., Zhang, F., Sun, D., Zhang, Z.H., Dong, S.W., Xu, J.Z.
Source: Brazilian Journal of Medical and Biological Research. July 2015 48(7)
Publisher Information: Associação Brasileira de Divulgação Científica, 2015.
Publication Year: 2015
Subject Terms: CTLA4, Mesenchymal stem cells, Immunomodulatory, Bone tissue engineering
More Details: 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.
Document Type: article
File Description: text/html
Language: English
ISSN: 0100-879X
DOI: 10.1590/1414-431x20154209
Access URL: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000700629
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Accession Number: edssci.S0100.879X2015000700629
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  Data: <i>Brazilian Journal of Medical and Biological Research</i>. July 2015 48(7)
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  Data: Associação Brasileira de Divulgação Científica, 2015.
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  Data: 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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