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

Abstract

Objective. Umbilical 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).Methods. We 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.Results. From 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.Conclusion. Our 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.Systemic lupus erythematosus (SLE) is an inflammatory disease with protean manifestations, ranging from relatively minor skin and joint symptoms to severe life-threatening major organ involvement, such as nephritis and neuropsychiatric complications (1). It is characterized by the presence of autoreactive T and B lymphocytes, with polyclonal activation of B cells and the consequent production of autoantibodies by plasma ClinicalTrials.gov identifier: NCT00698191.

Application of mesenchymal stem cells in paediatrics

“…All patients showed autoimmune disease remission and hence, presented a case for the discontinuation or reduction of the administered immunosuppressive drugs. Neither duration of the treatment nor patient observation period (from 12 to 18 months) indicated correlation with the appearance of serious side effects [38]. In this study, as in another study by Sun et al, the authors noted a disorder in the structure and functioning of the own MSCs of patients suffering from Systemic Lupus Erythematosus [38,39].…”

MicroRNA‐181a Regulates Local Immune Balance by Inhibiting Proliferation and Immunosuppressive Properties of Mesenchymal Stem Cells

“…Under stress conditions, MSCs decrease local inflammation and participate in tissue repair and regeneration by secreting cytokines, chemokines, and extracellular matrix proteins [3,4]. Previous data from our group and others demonstrated the immunosuppressive and anti-inflammatory effects of MSCs in the treatment of several animal disease models, including autoimmune diseases [5][6][7]. As a result of these unique qualities, MSCs are attractive candidates in stem cell-based strategies for tissue repair.…”

Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: Report of five cases

“…Significantly, this study demonstrated a therapeutic effect for at least 12 months, suggesting a longer lasting benefit compared to our cases. In another study, MSCs that had been derived from umbilical cords of nonrelated children were transplanted into 16 patients with SLE (14). The treatment led to meaningful clinical improvement and to a reduction of autoantibody titers.…”