Adult stem cell treatment of scleroderma

Provides an update of hematopoietic stem cell transplantation for systemic sclerosis from phase I/II studies and prospective randomized phase III trials, and introduces the concept of mesenchymal stem cells as potential therapy for autoimmune disease.

Around 170 transplanted systemic sclerosis patients are registered in Europe. Most received autologous, peripheral blood derived hematopoietic stem cell transplantation. Treatment-related mortality has fallen to 2.5% in the controlled trials compared with 12.5% in the first report in 2002. Over one-third of patients have experienced sustained remission. Two prospective randomized phase III studies are active: the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial in Europe and the Scleroderma Cyclophosphamide Or Transplant (SCOT) trial in the USA. Both have similar selection criteria, endpoint and control arms, but the SCOT trial uses radiation and less cyclophosphamide. So far, no unexpected toxicity has occurred. Reports produced in the past 12 months show reduction of skin collagen and reversal of microvascular remodelling, years after transplant. Bone marrow-derived mesenchymal stem cells from systemic sclerosis patients show in-vitro immunomodulatory properties equal to healthy controls.

Hematopoietic stem cell transplantation is currently being tested in prospective randomized controlled trials and appears to 'reset' autoimmunity in systemic sclerosis. Mesenchymal stem cells may have an immunomodulatory role in autoimmune disease.