Autoimmune diseases as stem cell disorders: normal stem cell transplant for their treatment (Review)

Using various animal models for autoimmune diseases, we have found that autoimmune diseases are stem cell disorders. The transplantation of normal hemopoietic stem cells (HSCs) can be used to treat autoimmune diseases, whereas the transplantation of abnormal HSCs from autoimmune-prone mice to normal mice leads to the induction of autoimmune diseases in recipients. To elucidate the differences between normal and abnormal HSCs, we have established a new method for purifying pluripotent-HSCs (P-HSCs), and have compared the qualitative differences. Although normal P-HSCs cannot proliferate under major histocompatibility complex (MHC)-incompatible microenvironments (stromal cells), abnormal P-HSCs can proliferate under such conditions. In addition, the proliferation of abnormal P-HSCs is much faster than that of normal P-HSCs. These findings indicate that abnormal P-HSCs are more resilient than normal P-HSCs. Therefore, we propose that allogeneic bone marrow transplantation (BMT) (not autologous BMT) should be applied to the treatment of autoimmune diseases. human data on BMT in autoimmune diseases is reviewed, and the conditions essential for successful BMT, including tolerance induction, are discussed.