Hematopoietic stem cell transplantation for autoimmune diseases: more than just prolonged immunosuppression

To summarize the current clinical experience in the use of autologous hematopoietic stem cell transplantation (HSCT) in autoimmune disease and to explore the concept of durable remission induction and tissue de-remodeling via restoration of normal niche function and "immune reset.'

Controlled clinical trials in systemic sclerosis, multiple sclerosis, and Crohn's disease as well as extensive uncontrolled trial and registry data have established the unique role of HSCT in selected cases. Although HSCT for multiple sclerosis and systemic sclerosis has recently entered several official treatment guidelines, mechanistic studies are few but indicate some possible modes of action, for example, increase of regulatory T cells. Toxicity of HSCT remains high but is improving with protocol modifications and more precise patient selection.

For the first time, it has been demonstrated that strategies exist which may permanently reprogram an autoaggressive immune system to one of self-tolerance independent of ongoing immunosuppression. In addition, some tissues have the capacity to repair damage via normal regenerative processes. The exact mechanism(s) as to how this is achieved in certain cases and not others are emerging. Such knowledge, together with adoption of recently developed less toxic and more targeted regimens from the hematology/oncology field may translate to a safer yet still effective treatment for autoimmune disease.