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Abstract Number: 2556

Allogenic Mesenchymal Stem Cells Transplantation Alleviates Clinical Sjögren’s Syndrome

Lingyun Sun1, Dandan Wang1, Junji Xu2 and Songlin Wang2, 1Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, 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

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Sjogren's syndrome and mesenchymal stem cells

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Session Information

Session Title: Sjögren's Syndrome II - Clinical

Session Type: Abstract Submissions (ACR)

Background/Purpose: 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. This study is undertaken to determine the safety and efficacy of allogenic mesenchymal stem cells (MSCs) 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) refractory to standard treatments were enrolled. Fresh umbilical cords (UC) were obtained from informed healthy mothers after normal deliveries. UC MSCs were expanded and infused intravenously (one million cells per kilogram of bodyweight per infusion). The clinical manifestations and laboratory parameters were compared pre- and post- MSCs transplantation (MSCT), with all patients completed 12 months follow up. Side effects were monitored during and post-MSCT.

 Results: All patients tolerated well with allogenic UCMSCT, and no adverse events occurred during or after MSCs infusion. Mean SS disease activity index (SSDAI) scores for all 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 (all P<0.05). Global assessment by visual analog scale (VAS) also improved at 1 month, and showed further ameliorations at 3, 6, and 12 months after UCMSCT. Unstimulated salivary flow rate increased significantly 2 weeks after UCMSCT (1.00 ± 0.78 ml/10 min at 2 weeks vs. 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 vs. baseline, n=11). This flow rate continued to increase on subsequent follow-up visits. Stimulated salivary flow rate 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 vs. 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, punctate sialectasias in the parotid gland declined, dilation of main duct was improved 1 year after UCMSCT, and excretory function was also partially restored. Serum levels of anti-SSA/Ro and anti-SSB/La decreased 1 month post-MSCT (P<0.001, n = 5). The mechanism studies showed that the frequency of Th17 cells decreased while Treg cells increased (P<0.05) after MSCT. Serum levels TGF-β increased and IL-17 decreased 1 month post-MSCT (P<0.05).

Conclusion: 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:

L. Sun,
None;

D. Wang,
None;

J. Xu,
None;

S. Wang,
None.

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