Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases

Experiments with animal models of autoimmune disease provided the rational and stimulus for the current, clinical studies of autologous stem cell transplantation for the treatment of a variety of severe, refractory, autoimmune diseases. The discoveries that led to the recognition of the key role of hematopoietic stem cells and the successful treatment of autoimmune diseases with bone marrow transplants are reviewed. The relevance of spontaneous and induced autoimmune disease models for the development of clinical treatment regimens is discussed. Most of the investigations with autologous stem cell transplantation have been performed with induced autoimmune disorders: in rats with adjuvant arthritis and in rats or mice with experimental, allergic encephalomyelitis, the current model for multiple sclerosis. The main aspects of this translational research were the conditioning regimens and the degree of T cell depletion of the graft as determinants of remission induction and the incidence of relapses. The emerging recommendations are compared with the outcome so far of the clinical studies.