ClinicalTrials.gov identifier: NCT00698191.
Systemic Lupus Erythematosus Clinical Studies
Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus†
Article first published online: 6 MAY 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 8, pages 2467–2475, August 2010
How to Cite
Sun, L., Wang, D., Liang, J., Zhang, H., Feng, X., Wang, H., Hua, B., Liu, B., Ye, S., Hu, X., Xu, W., Zeng, X., Hou, Y., Gilkeson, G. S., Silver, R. M., Lu, L. and Shi, S. (2010), Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis & Rheumatism, 62: 2467–2475. doi: 10.1002/art.27548
- Issue published online: 3 AUG 2010
- Article first published online: 6 MAY 2010
- Manuscript Accepted: 27 APR 2010
- Manuscript Received: 21 NOV 2009
- National Natural Science Foundation of China. Grant Numbers: 30972736, 30772014
- Jiangsu Province Science and Technology Achievement Transformation Foundation. Grant Number: BA2009124
- Chinese National 115 Supporting Program. Grant Number: 2008BAI59B02
- Jiangsu Province Natural Science Foundation. Grant Number: BK2009034
- Jiangsu Province 135 Talent Foundation. Grant Number: RC2007002
- Jiangsu Province Six Summit Talent Foundation
- Nanjing Public Health Bureau Key Medical Project. Grant Number: ZKX09025
Umbilical cord (UC)–derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE).
We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti–double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines.
From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3–28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1- and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths.
Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE.