Adult Stem Cell Treatment of Scleroderma

Alan Tyndall; Daniel E. Furst


Curr Opin Rheumatol. 2007;19(6):604-610. 

In This Article

Abstract and Introduction

Purpose of review: 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.
Recent findings: 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.
Summary: 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.

Immunosuppressive agents such as cyclophosphamide have long been used to treat autoimmune disease, but the dose is often limited by bone marrow suppression. Ten years ago several groups considered adopting the oncological approach of myeloablative therapy followed by haematological 'rescue' using either autologous or allogeneic hematopoietic stem cells to treat severe, therapy-resistant autoimmune disease. The concept was supported by animal model data,[1] suggesting tolerance induction in a rat arthritis model and cases of patients receiving an hematopoietic stem cell transplantation (HSCT) for conventional indications and in whom a coincidental autoimmune disease was improved or eradicated.[2]

After several international meetings,[3,4] consensus guidelines were developed and the first published case of a patient receiving an HSCT as treatment for an autoimmune disease alone was published in October 1996.[5] Since then, over 1000 patients have been transplanted for autoimmune disease, the majority within the context of phase I/II trials and more recently within phase III prospective randomized studies.

In the European Group for Blood and Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) database, 136 systemic sclerosis (SSc) patients are registered.


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