Lasting Benefits of IV Cellular Therapy in Lupus Patients

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Allogeneic Mesenchymal Stem Cell Transplantation in Severe and Refractory Systemic Lupus Erythematosus: 4 Years of Experience

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Article Information: Volume: 22 issue: 12, page(s): 2267-2277

First published online: December 1, 2013; Issue published: December 1, 2013

Abstract

Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitors and are capable of differentiating into several tissues of mesenchymal origin. We have shown that bone marrow-derived MSCs from both SLE patients and lupus-prone MRL/lpr mice are defective structurally and functionally. Here we observe the long-term safety and efficacy of allogeneic MSC transplantation (MSCT) in treatment-resistant SLE patients. Eighty-seven patients with persistently active SLE who were refractory to standard treatment or had life-threatening visceral involvement were enrolled. Allogeneic bone marrow or umbilical cord-derived MSCs were harvested and infused intravenously (1 × 106 cells/kg of body weight). Primary outcomes were rates of survival, disease remission and relapse, as well as transplantation-related adverse events. Secondary outcomes included SLE disease activity index (SLEDAI) and serologic features. During the 4-year follow-up and with a mean follow-up period of 27 months, the overall rate of survival was 94% (82/87). Complete clinical remission rate was 28% at 1 year (23/83), 31% at 2 years (12/39), 42% at 3 years (5/12), and 50% at 4 years (3/6). Rates of relapse were 12% (10/83) at 1 year, 18% (7/39) at 2 years, 17% (2/12) at 3 years, and 17% (1/6) at 4 years. The overall rate of relapse was 23% (20/87). Disease activity declined as revealed by significant changes in the SLEDAI score, levels of serum autoantibodies, albumin, and complements. A total of five patients (6%) died after MSCT from non-treatment-related events in the 4-year follow-up, and no transplantation-related adverse event was observed. Allogeneic MSCT resulted in the induction of clinical remission and improvement in organ dysfunction in drug-resistant SLE patients.

Authors

Dandan WangHuayong ZhangJun LiangXia LiXuebing FengHong WangBingzhu HuaBujun Liu Liwei LuGary S. GilkesonRichard M. SilverWanjun ChenSongtao ShiLingyun Sun

*Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, P. R. China†Department of Pathology and Microbiology, Center of Infection and Immunology, Hong Kong University, Hong Kong, China‡Division of Rheumatology, Medical University of South Carolina, Charleston, SC, USA§Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA¶Center for Craniofacial Molecular Biology, University of Sothern California School of Dentistry, Los Angeles, CA, USA Corresponding Author: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, P. R. China. Tel: +86-25-8310-5219; Fax: +86-25-8310-5209; E-mail: lingyunsun2001@yahoo.com.cn or lingyunsun2012@163.com