Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Wiley - Tập 62 Số 8 - Trang 2467-2475 - 2010
Lingyun Sun1, Dandan Wang1, Jun Liang1, Huayong Zhang1, Xuebing Feng1, Hong Wang1, Bingzhu Hua1, Bujun Liu1, Shengqin Ye2, Xiang Hu2, Wenrong Xu3, Xiaofeng Zeng4, Yayi Hou5, Gary S. Gilkeson6, Richard M. Silver6, Liwei Lu7, Songtao Shi8
1The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
2Stem Cell Center of Jiangsu Province, Taizhou, China
3Jiangsu University, Zhenjiang, China
4Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
5Nanjing University Medical School, Nanjing, China
6Medical University of South Carolina, Charleston
7University of Hong Kong, Hong Kong, China
8University of Southern California School of Dentistry, Los Angeles.

Tóm tắt

AbstractObjectiveUmbilical 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).MethodsWe 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.ResultsFrom 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.ConclusionOur 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.

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Wiley

Tập 62 Số 8

2467-2475

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