hCTLA4-Gene Modified Human Bone Marrow–Derived Mesenchymal Stem Cells as Allogeneic Seed Cells in Bone Tissue Engineering

Abstract

Immune rejection of heterogeneic seed cells, even of low antigenicity human bone marrow derived mesenchymal stem cells (hBMMSCs), remains an obstacle for bone tissue engineering. It is still a question how to transfer the gene of human cytotoxic T lymphocyte–associated antigen 4-Ig (CTLA4-Ig), a well-known ligand for CD80/CD86, to hBMMSCs to prolong survival time while not interfering with their osteogenesis in vivo. Our data, for the first time, clearly demonstrate that CTLA4-Ig gene modified hBMMSCs could normally differentiate to osteoblasts in vitro, significantly inhibit immune response in the model of mixed lymphocyte culture, and survive until bone tissue formed in vivo. Thus, CTLA4Ig gene-modified hBMMSCs might be promising seed cells for bone tissue engineering.