Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus

Abstract

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.

Multipotent adult progenitor cells improve the hematopoietic function in myelodysplasia

“…Improvement in cytopenias after MSC treatment has also been seen in mouse models of acute radiation syndrome [33,34]. In addition, MSC infusion in systemic lupus erythematosus patients with refractory cytopenias resulted in increased blood cell counts, which might have been associated with the reconstitution of regulatory T and Th17 cells [35].…”

Mesenchymal stromal cells and rheumatic disorders

“…Initially three reports appeared in the same year; one with two patients who failed to respond to autologous bone marrow derived MSC clinically despite an increase in circulating Treg cells [16] and two other reports, both from the same centre, showing clinical improvement in 15 patients treated with allogeneic bone marrow derived MSC [17] and also in 16 similar patients who had received allogeneic umbilical derived MSC [18]. Further reports from the same centre showed improvement in four SLE patients with pulmonary haemorrhage [19] using umbilical cord derived MSC and 35 with refractory cytopenias [20] using either allogeneic bone marrow or umbilical cord MSC. Between 2012 and 2014 the same group has published 4 further SLE case series, 87 clinically heterogenoeus patients [21], 58 refractory nephritis patients [22], 40 mostly refractory nephritis patients [23] and a further 81 refractory nephritis patients [24].…”

Impaired B Cell Inhibition by Lupus Bone Marrow Mesenchymal Stem Cells Is Caused by Reduced CCL2 Expression

“…After 3 d of culture, nonadherent cells were removed and the medium was changed twice weekly thereafter. Once 80% confluence was reached, adherent cells were replaced at a density of 10 4 cells/cm 2 for expansion (26,29).…”

“…We and others have shown that lupus BMMSCs grow slowly with early signs of senescence, and exhibit some disorders in cytoskeleton and ultrastructure (23)(24)(25). In addition, accumulating evidence has indicated that allogeneic normal MSCs, rather than autologous MSC transplantation (MSCT), are more effective in treating lupus in preclinical animal studies and SLE patients (26)(27)(28)(29), which suggests that lupus MSCs have a deficiency in suppressing SLE inflammation. However, whether lupus MSCs are functionally impaired in inhibiting normal B cells remains elusive.…”