Apoptotic cells in allogeneic hematopoietic stem cell transplantations: turning trash into gold

Allogeneic hematopoietic stem cell transplantation (HST) is an important therapeutic option for various malignant and nonmalignant conditions. HST during first remission offers the best cure for patients for whom conventional chemotherapy alone is not sufficient. Yet, in spite of the high curative potential and recent advances in this treatment modality, it remains limited by transplant related toxicity and grant-versus-host disease (GVHD). Apoptotic cells, which used to be regarded as immunologically bland, are now recognized as important modulators of immune responses. Taking into account the immunological properties of apoptotic cells and the nature of the side effects of HST, they have been administered simultaneously with hematopoietic stem cells in experimental transplantation models, in anticipation of improved outcome. Under these conditions, engraftment and full-donor chimerism are facilitated without significant generation of anti-apoptotic cell auto-antibodies. In addition they prevent alloimmunization, up-regulate T regulatory cells and reduce both the frequency and the severity of GVHD. These favorable effects require host macrophages and donor bone marrow plasmatoid dendritic cells, and are associated with tumor growth factor-beta (TGF-beta) production. To summarize, apoptotic cells can play a crucial role in the setting of transplantations, and may be viewed as turning trash into gold. Clinical studies are underway.