CTLA4 enhances the osteogenic differentiation of allogeneic human
mesenchymal stem cells in a model of immune activation |
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| Authors: | F. Dai F. Zhang D. Sun Z.H. Zhang S.W. Dong J.Z. Xu |
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| Affiliation: | 1.National and Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China;2.Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China |
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| Abstract: | ![]()
Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasinginterest for their broad clinical therapy applications. Despite this, many studieshave shown that allo-MSCs are associated with a high rate of graft rejection unlessimmunosuppressive therapy is administered to control allo-immune responses. CytotoxicT-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on Tcells that mediates the inhibition of T-cell function. Here, we investigated theosteogenic differentiation potency of allo-MSCs in an activated immune system thatmimics the in vivo allo-MSC grafting microenvironment and exploredthe immunomodulatory role of the helper T cell receptorCTLA4 in thisprocess. We found that MSC osteogenic differentiation was inhibited in the presenceof the activated immune response and that overexpression of CTLA4 inallo-MSCs suppressed the immune response and promoted osteogenic differentiation. Ourresults support the application of CTLA4-overexpressing allo-MSCs inbone tissue engineering. |
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| Keywords: | CTLA4 Mesenchymal stem cells Immunomodulatory Bone tissue engineering |
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