Background Umbilical cord (UC) derived mesenchymal stem cells (MSCs) have shown safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE) in our single-centre pilot study.
Objectives The present multicentre clinical trial was undertaken in China to assess the efficacy and safety of allogenic UC MSCs transplantation (MSCT) in active SLE patients.
Methods Forty patients (aged ≥16 years) with active SLE (SLE Disease Activity Index >6) were enrolled from 4 clinical centres in China. All patients gave informed consents before transplantation, and allogenic UC MSCs were infused intravenously on days 0 and 7. Adverse event was monitored during and after MSCs transplantation. Primary efficacy endpoints were major clinical response (MCR), partial clinical response (PCR) and relapse at 6 and 12 months. Secondary endpoints were improvement in SLEDAI score, British Isles Lupus Assessment Group (BILAG) score, serum levels of creatinine, urea nitrogen, complements and albumin pre- and post-MSCT.
Results Fourteen and fifteen patients achieved MCR (14/40, 35.0%) and PCR (15/40, 37.5%) at 6 months follow-up, respectively. Three and four patients experienced disease relapse at 9 (7.5%) and 12 (10%) months follow-up, respectively, after a prior clinical response. SLEDAI score significantly decreased at 3 (7.43±3.93), 6 (6.30±3.63), 9 (6.40±3.84) and 12 months (6.48±3.52) follow-up (P all <0.05 vs. baseline 10.83±4.63). Total BILAG score markedly decreased 3 months after MSCT, and continued to decrease in the following visit times. BILAG score for renal and hematopoietic system significantly improved. For those with lupus nephritis, 24-hour proteinuria declined after transplantation, with statistical differences at 9 (1.24±1.09 mg) and 12 months (1.41±1.33 mg, P<0.05 vs. baseline 2.24±1.43 mg). Serum creatinine and urea nitrogen decreased to the lowest level at 6 months, while slightly increased at 9 and 12 months due to the 7 relapsed cases. Additionally, Serum levels of albumin, complements 3 and 4 increased after MSCT, peaked at 6 months visit, then slight declined at 9 and 12 months. Serum anti-nuclear antibody (ANA) and anti-double strand DNA (dsDNA) antibody decreased after MSCT, with statistical differences at 3 months follow-up. Furthermore, hemoglobin and platelet counts increased after MSCT in those with hematopoietic involvement. UC-MSCT was well tolerated and no adverse event was observed.
Conclusions Our findings indicate that UC MSCT results in satisfactory clinical responses in SLE. However, several cases experienced disease relapse after 6 months visit, which suggests the necessity for repeated MSCT after 6 months in some patients.
Disclosure of Interest None Declared