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Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy

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Abstract

Allogeneic mesenchymal stem cell transplantation (MSCT) has been shown to be clinically efficacious in the treatment of various autoimmune diseases. Here, we analyzed the role of allogeneic MSCT to induce renal remission in patients with active and refractory lupus nephritis (LN). This is an open-label and single-center clinical trial conducted from 2007 to 2010 in which 81 Chinese patients with active and refractory LN were enrolled. Allogeneic bone marrow- or umbilical cord-derived mesenchymal stem cells (MSCs) were administered intravenously at the dose of 1 million cells per kilogram of bodyweight. All patients were then monitored over the course of 12 months with periodic follow-up visits to evaluate renal remission, as well as possible adverse events. The primary outcome was complete renal remission (CR) and partial remission (PR) at each follow-up, as well as renal flares. The secondary outcome included renal activity score, total disease activity score, renal function, and serologic index. During the 12-month follow-up, the overall rate of survival was 95 % (77/81). Totally, 60.5 % (49/81) patients achieved renal remission during 12-month visit by MSCT. Eleven of 49 (22.4 %) patients experienced renal flare by the end of 12 months after a previous remission. Renal activity evaluated by British Isles Lupus Assessment Group (BILAG) scores significantly declined after MSCT (mean ± SD, from 4.48 ± 2.60 at baseline to 1.09 ± 0.83 at 12 months), in parallel with the obvious amelioration of renal function. Glomerular filtration rate (GFR) improved significantly 12 months after MSCT (mean ± SD, from 58.55 ± 19.16 to 69.51 ± 27.93 mL/min). Total disease activity evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores also decreased after treatment (mean ± SD, from 13.11 ± 4.20 at baseline to 5.48 ± 2.77 at 12 months). Additionally, the doses of concomitant prednisone and immunosuppressive drugs were tapered. No transplantation-related adverse event was observed. Allogeneic MSCT resulted in renal remission for active LN patients within 12-month visit, confirming its use as a potential therapy for refractory LN.

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Acknowledgments

The authors thank Professor Wanjun Chen (Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, MD, USA) for helpful comments. This work was supported by the Major International (Regional) Joint Research Project (no. 81120108021, to Dr. Sun), National Natural Science Foundation of China (no. 81273304, to Dr. Sun), and Jiangsu Province Kejiao Xingwei Program (to Dr. Sun), Jiangsu Provincial Natural Science Foundation (BK20140098, to Dr. Wang), and Jiangsu Provincial Health Department Youth Foundation (Q201411, to Dr. Wang)and National Natural Science Foundation of China (no. 81302557, to Dr. Gu).

Conflict of interest

Fei Gu, none; Dandan Wang, none; Huayong Zhang, none; Xuebing Feng, none; Gary S. Gilkeson, none; Songtao Shi, none; Lingyun Sun, none.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China

    Fei Gu, Dandan Wang, Huayong Zhang, Xuebing Feng & Lingyun Sun

  2. Devision of Rheumatology, Medical University of South Carolina, Charleston, USA

    Gary S. Gilkeson

  3. Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, SC, USA

    Songtao Shi

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  1. Fei Gu
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Correspondence to Lingyun Sun.

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Fei Gu and Dandan Wang contributed equally to this paper.

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Supplementary Fig 1

The comparison of 24-hour proteinuria between bone marrow and umbilical cord derived MSC transplantations. (PDF 38 kb)

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Gu, F., Wang, D., Zhang, H. et al. Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. Clin Rheumatol 33, 1611–1619 (2014). https://doi.org/10.1007/s10067-014-2754-4

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  • DOI: https://doi.org/10.1007/s10067-014-2754-4

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