Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L

Christopeit, Maximilian; Schendel, Marit; Föll, Jürgen; Müller, Lutz; Keyßer, Gernot; Behre, Gerhard

doi:10.1038/sj.leu.2404996

Cited by 135 publications

(82 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential, together with their effects on immune responses, make them a promising therapeutic tool for severe refractory autoimmune diseases. MSCs have already been used in clinical trials as a treatment for acute graft-versus-host disease following allogeneic HSCT (25,26) and for autoimmune diseases such as systemic sclerosis (27) and type 1 diabetes mellitus (28).…”

Section: Discussionmentioning

confidence: 99%

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

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

425

310

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

425

310

View full text Add to dashboard Cite

show abstract

“…Transplanted stem cells may potential together with their effects on immune responses make them promising therapeutic tools in several human diseases, including autoimmune diseases, endocrine diseases, and neurological disorders. MSCs have already been used in clinical trials as a treatment for acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (104,105) and for autoimmune diseases such as systemic sclerosis (106). Table 1 summarizes the current pediatric and adult trials using hUCMSCs for neurological disorders described in clinicaltrials.gov in November 2011.…”

Section: Effect Of Huc-mscs In Animal Models Of Perinatal Brain Injurymentioning

confidence: 99%

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

2012

View full text Add to dashboard Cite

“…Recent studies have emphasized the immunomodulatory functions of MSCs, making them important candidates for the treatment of autoimmune conditions including acute GVHD, following allogeneic hemopoietic SCT, 12,13 systemic sclerosis 14 and Type 1 diabetes mellitus. 15 Our previous data have indicated that allogeneic MSCT was a feasible and safe therapy in patients with refractory SLE 8,9 and drug-resistant polymyositis and dermatomyositis.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus

Wang

Liang

et al. 2012

Bone Marrow Transplant

View full text Add to dashboard Cite

Our previous data have revealed that proteinuria, antinuclear antibodies and anti-dsDNA antibodies in refractory systemic lupus erythematosus (SLE) reduced after MSC infusion. This study focused on the roles of mesenchymal SCT (MSCT) in SLE patients with refractory cytopenia. Thirty-five SLE patients with refractory cytopenia were enrolled in a MSCT trial. Hematological changes of pre-and post-transplantation were evaluated. Mechanisms for MSCT effects focused on the analysis of percentage of regulatory T cells (Treg) and Th17. The results showed that in 35 SLE patients, 20 patients had leukopenia, 24 with anemia or thrombocytopenia. The average follow-up period after MSCT was 21 months (range 6-45 months). Significant improvements in blood cell count were found after MSCT for most patients, in parallel with the decline of disease activity. Clinical remission was accompanied by increased Treg and decreased Th17. Two patients died of uncontrolled disease recurrence after infection, whereas no adverse events related to transplantation was observed. The result suggested that MSCT could reverse hematological aberration in SLE patients with refractory cytopenia, which might be associated with reconstitution of Treg and Th17. Longer follow-up and clinical larger-scale controlled study, as well as the exact mechanism exploration, will need further investigations.

show abstract

Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L

Cited by 135 publications

References 6 publications

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

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

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus

Contact Info

Product

Resources

About