title: CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation.
abstract: 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.
authors.affiliation: Department of Orthopedics, National and Regional United Engineering Laboratory of Tissue Engineering, Third Military Medical University, Chongqing, China.
authors.forename: F
authors.initials: F
authors.lastname: Dai
authors.affiliation: Department of Orthopedics, National and Regional United Engineering Laboratory of Tissue Engineering, Third Military Medical University, Chongqing, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, National and Regional United Engineering Laboratory of Tissue Engineering, Third Military Medical University, Chongqing, China.
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, National and Regional United Engineering Laboratory of Tissue Engineering, Third Military Medical University, Chongqing, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: School of Biomedical Engineering, Department of Biomedical Materials Science, Third Military Medical University, Chongqing, China.
authors.forename: S W
authors.initials: SW
authors.lastname: Dong
authors.affiliation: Department of Orthopedics, National and Regional United Engineering Laboratory of Tissue Engineering, Third Military Medical University, Chongqing, China.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Xu
mesh_terms: D015153:Blotting, Western; D060908:CTLA-4 Antigen / Q000032:analysis / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D010012:Osteogenesis / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D023822:Tissue Engineering; D014184:Transplantation, Homologous
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007166:Immunosuppressive Agents