Adult stem cells in the treatment of autoimmune diseases

Adult stem cells in the treatment of autoimmune diseases

Advance Access publication

 

Source

Rheumatology 2006;45:1187–1193    doi:10.1093/rheumatology/kel158

J. M. van Laar1 and A. Tyndall2

 

Abstract

During the past 10 yrs, over 700 patients suffering from severe autoimmune disease (AD) have received an autologous haematopoietic stem cell transplant as treatment of their disorder with durable remission being obtained in around one-third. The most commonly transplanted ADs have been systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. A fewer number of patients have received an allogeneic transplant. The initially reported overall treatment-related mortality of 7% has since fallen, with no further cases being reported in systemic sclerosis or multiple sclerosis in the past 3 yrs. This is thought to be due to more careful patient selection.The phase I/II data has led to currently running prospective randomised trials in systemic sclerosis, multiple sclerosis and systemic lupus erythematosus in Europe and North America. Immune reconstitution data suggests a ‘resetting’ of autoimmunity in those patients achieving stable remission, rather than simply prolonged immunosuppression. Recent results from in vitro experiments, animal models and early human experience in severe acute graft vs host disease suggest that multipotent mesenchymal stromal cells obtained from the bone marrow and expanded ex vivo , may exert a clinically useful immunomodulatory effect. Such cells are immune privileged and apparently of low toxicity. Further characterization of these cells and consideration of their possible clinical application in AD is underway.

 

Conclusion

The past decade has seen the introduction of many agents, especially biologics, which have allowed a more successful control of AD manifestations. However, the elusive aim of tolerance induction has not yet been achieved. It could be that through harnessing the complex and multifaceted potential of cellular-based therapies, especially HSCT, a ‘resetting‘ of autoaggressive immune reactions while maintaining protective immunity will be possible. In addition, the anti-proliferative and immunomodulatory properties of MSCs combined with their immunological privilege and seemingly low toxicity may offer a new strategy for controlling and protecting vital organs from inflammatory, destructive autoimmune reactions.

 

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