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SAT0194 Allogenic mesenchymal stem cells transplantation alleviates clinical sjögren’s syndrome
  1. D. Wang1,
  2. H. Zhang1,
  3. X. Li1,
  4. J. Xu2,
  5. S. Wang2,
  6. L. Sun1
  1. 1Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing
  2. 2Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China

Abstract

Background Sjögren’s syndrome (SS) is a systemic autoimmune disease that is characterized by dry mouth and dry eyes. Currently, treatment of SS is difficult and challenging.

Objectives To determine the safety and efficacy of allogenic mesenchymal stem cells (MSC) transplantation in SS patients.

Methods Twenty-four patients with primary SS (23 females and 1 male; age from 27 to 68 years old, mean 45 years old), that were refractory to standard treatments, were enrolled. Fresh umbilical cords (UC) were obtained from informed healthy mothers after normal deliveries. UC MSC were prepared by the Stem Cell Center of Jiangsu Province, China. Allogenic UC MSC were infused intravenously (one million cells per kilogram of body weight per infusion). The clinical manifestations and laboratory parameters were compared pre- and post- MSC transplantation (MSCT), with all patients completing 12 months follow-up. Side effects were monitored all the time during and post-MSCT.

Results All patients tolerated well with allogenic UC MSCT, and no adverse events occurred during or after MSC infusion. Mean SS disease activity index (SSDAI) scores of all the 24 patients decreased from 5.63±1.44 (baseline) to 4.33±1.79 at 1 month, 4.08±1.44 at 3 months, 3.46±1.18 at 6 months, and 3.08±1.21 at 12 months after MSCT (all P<0.05). Global assessment by visual analog scale (VAS) also improved 1 month after UC MSCT, and showed further ameliorations 3, 6, and 12 months later. Unstimulated salivary flow rate of all 11 patients with symptoms of xerostomia increased significantly 2 weeks after UC MSCT (1.00±0.78 ml/10 min at 2 weeks versus 0.63±0.73 ml/10min at baseline, P <0.001, n=11) and showed a 2-fold increase at 1 month (1.26±1.02, P <0.001 versus baseline, n=11). This flow rate continued to increase on subsequent follow-up. Stimulated salivary flow rate of these 11 patients also significantly increased after MSCT (P =0.008 at 2 weeks, P =0.043 at 1 month, P =0.016 at 3 months, P =0.017 at 6 months and P =0.016 at 12 months versus baseline, n=11). The determination of modified treatment emergent symptom scale (TESS) score decreased at 2 weeks visit, and was maintained at this low level on subsequent visits. Furthermore, sialogram of the parotid gland and its excretory function were analyzed by the same radiologist and rheumatologist. Punctate sialectasias in the parotid gland slightly declined, dilation of main duct was improved 1 year after UC MSCT, and excretory function was also partially restored. Anti-SSA/Ro in serum decreased from 84.76±62.19 unit/ml at baseline to 0.51±0.22 unit/ml 1 month post-MSCT (P<0.001, n=5), and anti-SSB/La in serum decreased from 146.62±83.08 unit/ml at baseline to 52.61±38.67 unit/ml 1 month post-MSCT (P<0.001, n=4). The mechanism studies showed that the frequency of Th17 cells decreased 3 months post-MSCT (P=0.01), while the percentage of regulatory T cell (Treg) increased (P=0.013). Serum levels of TGF-β increased from 15.65±1.95 pg/ml at baseline to 17.68±3.67 pg/ml 1 month post-MSCT (P=0.05, n=4), and the levels of IL-17 decreased from 39.25±3.46 pg/ml at baseline to 37.52±0.66 1 month post-MSCT (P=0.048, n=4).

Conclusions Allogenic UC MSCT is safe and results in amelioration of disease activity. These data provide a foundation for conducting allogenic UC MSCT for SS patients.

Disclosure of Interest None Declared

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