Background Umbilical cord (UC) derived mesenchymal stem cells (MSCs) show immunoregulatory properties on various immune cells and display clinical effect on lots of autoimmune disease like systemic lupus erythematosus (SLE).
Objectives The aim of this study is to investigate the effect of SLE environment on UC MSCs and to observe the possible serum biomarker to predict the therapeutic effect.
Methods UC MSCs were co-cultured with peripheral blood mononuclear cells (PBMC) from active lupus patients at a ratio of 1:4. The proliferation, apoptosis and surface markers of UC MSCs were observed. UC MSCs functional molecules were assessed by real-time PCR and the signaling pathways were analyzed by western blot. Different recombinant cytokines were used to stimulate UC MSCs in vitro and the functional factors were determined by real-time PCR. In the last, twenty-six patients with SLE, refractory to conventional therapies, were given UC MSCs transplantation. The clinical effect was followed-up for one year to classify responder and non-responder groups, and baseline serum cytokines were analyzed by ELISA.
Results The co-culture of lupus patients PBMC had no effect on UC MSCs surface markers and apoptosis, but promoted MSCs proliferation. Lupus PBMC were more prone to stimulate UC MSCs to secret VEGF as well as CXCL-12, compared to PBMC from normal controls. Furthermore, lupus PBMC activated Akt, IκB and Stat5 signaling pathways in UC MSCs but not affect Erk1/2 and Smad1/5/8 pathways. When stimulated by different cytokines, we found that interferon γ (IFN-γ) was still the most important cytokine to induce IDO1 as well as IDO2 productions in UC MSCs; both had dose-dependent manners. Moreover, our clinical study showed that baseline higher levels IFN-γ might predict a good response to MSCs transplantation in active lupus patients.
Conclusions Baseline IFN-γ levels may predict clinical response to MSCs therapy for active lupus patients, which will help us to choose appropriate patient for clinical transplantation.
Disclosure of Interest None declared