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

Abstract

IntroductionIn 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.MethodsForty 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.ResultsThe 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.ConclusionUC-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 registryClinicalTrials.gov identifier: NCT01741857. Registered 26 September 2012.

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

“…In this context, a GMP-compliant method was PL as a substitute for FBS. While other isolation and expansion protocols of UC-MSCs were proposed [33,35], the method we adopted allows a minimal manipulation of the UC, thus avoiding the possible initial selection of cell subpopulations [6] yielding the isolation of high-grade MSCs [36].…”

Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study

“…The eligibility criteria included treatment-refractory and active disease, as well as a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of more than eight or at least one British Isles Lupus Assessment Group (BILAG) grade A or at least two BILAG grade B manifestations. Refractory treatment meant lack of response to treatment with monthly intravenous pulse cyclophosphamide (CYC, 500-750 mg/ m 2 ) for C6 months or lack of response to treatment with oral mycophenolate mofetil (MMF, C1000 mg/day) or leflunomide (20 mg/day) for C3 months, or continued daily doses of C20 mg of prednisone or its equivalent [15,16]. Patients were excluded from the study if they had the following conditions: (1) infection: including pneumonia, pulmonary tuberculosis, hepatitis, skin infection, central nervous system infection; (2) heart failure: New York Heart Association functional classification III or IV;…”

RETRACTED ARTICLE: Purified umbilical cord derived mesenchymal stem cell treatment in a case of systemic lupus erythematosus

“…In that study, the authors examined several published studies which used MSC from various sources and demonstrated efficacy [4]. A more recent evaluation completed in 2014 demonstrated that umbilical cord derived MSC resulted in satisfactory clinical response but the response was time limited to approximately 6 months [5]. MSC therapy has the advantages of modulating the inflammatory cascade while stabilizing the progenitor cell lines thereby reducing the inflammatory and autoimmune dysfunction.…”