Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study

Abstract

Introduction: In our present single-center pilot study, umbilical cord (UC)-derived mesenchymal stem cells (MSCs) had a good safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE). The present multicenter clinical trial was undertaken to assess the safety and efficacy of allogeneic UC MSC transplantation (MSCT) in patients with active and refractory SLE.

Methods: Forty patients with active SLE were recruited from four clinical centers in China. Allogeneic UC MSCs were infused intravenously on days 0 and 7. The primary endpoints were safety profiles. The secondary endpoints included major clinical response (MCR), partial clinical response (PCR) and relapse. Clinical indices, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, British Isles Lupus Assessment Group (BILAG) score and renal functional indices, were also taken into account.

Results: The overall survival rate was 92.5% (37 of 40 patients). UC-MSCT was well tolerated, and no transplantation-related adverse events were observed. Thirteen and eleven patients achieved MCR (13 of 40, 32.5%) and PCR (11 of 40, 27.5%), respectively, during 12 months of follow up. Three and four patients experienced disease relapse at 9 months (12.5%) and 12 months (16.7%) of follow-up, respectively, after a prior clinical response. SLEDAI scores significantly decreased at 3, 6, 9 and 12 months follow-up. Total BILAG scores markedly decreased at 3 months and continued to decrease at subsequent follow-up visits. BILAG scores for renal, hematopoietic and cutaneous systems significantly improved. Among those patients with lupus nephritis, 24-hour proteinuria declined after transplantation, with statistically differences at 9 and 12 months. Serum creatinine and urea nitrogen decreased to the lowest level at 6 months, but these values slightly increased at 9 and 12 months in seven relapse cases. In addition, serum levels of albumin and complement 3 increased after MSCT, peaked at 6 months and then slightly declined by the 9- and 12-month follow-up examinations. Serum antinuclear antibody and anti-double-stranded DNA antibody decreased after MSCT, with statistically significant differences at 3-month follow-up examinations.

Conclusion: UC-MSCT results in satisfactory clinical response in SLE patients. However, in our present study, several patients experienced disease relapse after 6 months, indicating the necessity to repeat MSCT after 6 months.

Trial registry: ClinicalTrials.gov identifier: NCT01741857. Registered 26 September 2012.

Figure 1

Graphs illustrate changes in clinical status before and after umbilical cord mesenchymal stem cell transplantation. Changes in clinical status from before umbilical cord mesenchymal stem cell transplantation (MSCT) and afterward were assessed based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (A) and total British Isles Lupus Assessment Group (BILAG) score (B). **P < 0.01 versus before MSCT. ***P < 0.001 versus before MSCT. Error bars mean SD values.

Figure 2

Graphs illustrate improvement after allogeneic umbilical cord mesenchymal stem cell transplantation. Improved levels serum albumin (A) and complement 3 (C3) (B) in lupus patients refractory to other treatments. Serum levels of anti-double-stranded DNA (anti-sDNA) antibody (C) and antinuclear antibody (ANA) (D) decreased after MSC infusions. *P < 0.05 versus before mesenchymal stem cell transplantation (MSCT). Error bars mean SD values.

Figure 3

Graphs illustrate marked improvement in renal system after umbilical cord mesenchymal stem cell transplantation. (A) British Isles Lupus Assessment Group (BILAG) score improved over time. Twenty-four hours after umbilical cord mesenchymal stem cell transplantation (MSCT), declines were observed in proteinuria (B), serum creatinine (C) and blood urea nitrogen (BUN) (D). BILAG scores for the hematopoietic (E) and cutaneous (F) systems were ameliorated after MSCT. *P < 0.05 versus before MSCT. **P < 0.01 versus before MSCT. Error bars mean SD values.