Autoimmune diseases as 'stem cell disorders'

Abstract

Using various animal models for autoimmune diseases, we have found that bone marrow transplantation (BMT) can be used to treat not only systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis IRA), but also organ-specific autoimmune diseases such as immune thrombocytopenic purpura (ITP) and insulin-dependent diabetes mellitus (IDDM). We have also found that the transplantation of hemopoietic stem cell (HSC)-enriched populations from autoimmune-prone mice to normal mice induces autoimmune diseases in the recipients. These findings have recently been confirmed in humans; BMT can be used to treat autoimmune diseases such as RA, Crohn's disease and ulcerative colitis (UC), whereas autoimmune diseases such as Graves' disease and ITP have been transferred from donors to recipients by BMT. Based on these findings, we have proposed that autoimmune diseases are 'stem cell disorders' to elucidate the differences between normal and abnormal HSCs, we have very recently established a new method for purifying pluripotent HSCs (P-HSCs). Using P-HSCs purified by our method, we have compared normal and abnormal P-HSCs, and found that qualitative differences exist between them both in vive and in vitro; although normal P-HSCs do not readily proliferate in major histocompatibility complex (MHC)-incompatible microenvironments, abnormal P-HSCs show a marked proliferative response even in the allogeneic environments. Abnormal P-HSCs are thus more 'resilient' than normal P-HSCs.