Abstract
Blood transfusion, organ and bone marrow transplantation and allogeneic tissue grafting create the potential for significant immunological challenges through the introduction of non-genetically identical major (HLA) and minor histocompatibility antigens (“allo-antigens”) into the body. Strategies to avoid the complications of immune responses against allo-antigens (transfusion reactions, rejection and graft versus host disease) include HLA matching, immunosuppressive therapies and immune tolerance promoting protocols. In the case of allogeneic mesenchymal stem/stromal cells (allo-MSC), it was initially believed that their combined properties of low HLA expression and inherent immune modulatory functions would render them invisible to the host immune system and, therefore, capable of being permanently accepted without further interventions. For clinical indications such as bone and tendon repair, in which permanent engraftment of allo-MSC or MSC-derived tissue constructs is particularly desirable, this model of “immune privilege” seemed almost too good to be true – and indeed, a decade of experimental research in this area has now convincingly demonstrated that allo-MSC typically elicit cellular (T-cell) and humoral (B-cell/antibody) immune responses in immunocompetent hosts – raising concern about their safety and long-term efficacy in human conditions. However, questions related to the immunogenicity of allo-MSC have evolved beyond a simple yes/no scenario to involve interesting observations and concepts about the potency, diversity, duration, functional characteristics and even potential clinical benfits of immunological responses to allo-MSC. In this presentation, I will summarise and critically evaluate current understanding of allo-MSC immunogenicity under experimental and clinical trial conditions with an emphasis on the implications for orthopaedic therapeutics.
