Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study

Frontiers in Immunology

Carmen L. K. Rebelatto¹  Alexandra C. Senegaglia¹  Debora R. Daga¹  Paulo R. S. Brofman²  Leandra Santos Baptista³  Jessica P. Moreira⁴  Ronir R. Luiz⁴  Maria de Fátima C. Pereira⁵  Sergio A. Dib⁶  Monica A. L. Gabbay⁶  Debora B. Araujo⁷  Joana R. Dantas⁷  Angelo Maiolino⁸  Karina R. Silva⁹  Lenita Zajdenverg^1,10  Débora L. Souto^1,10  José E. P. Oliveira^1,10  Melanie Rodacki^1,10  Cesar S. Claudio-Da-Silva^1,11  Carlos E. B. Couri^1,12 

[1] 0Core Cell Technology, Pontifical Catholic University of Paraná, Curitiba, Brazil;1Surgical Clinic D at University of Sao Paulo, Core Cell Technology, Pontifical Catholic University of Paraná, Curitiba, Brazil;2Multidisciplinary Center for Biological Research (Numpex-Bio), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Biostatistics Department, Institute of Public Health Studies, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Clinical Pathology Service, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Department of Stem Cell Therapy, Federal University of São Paulo (UNIFESP), São Paulo, Brazil;Federal University of Rio de Janeiro, Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Hematology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Laboratory of Tissue Bioengineering, National Institute of Metrology, Quality and Technology (Inmetro), Rio de Janeiro, Brazil;Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Plastic Surgery Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;University of São Paulo, São Paulo, Brazil;

关键词: type 1 diabetes;    pancreatic function;    transplant;    adipose tissue-derived stromal/stem cells;    vitamin D;   

DOI  :  10.3389/fimmu.2020.00993

来源: DOAJ

【 摘 要 】

Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D.Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3).Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (−4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83).Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D.ClinicalTrials.gov registration: NCT03920397.

【 授权许可】

Unknown