AUTHOR=Araujo Debora B. , Dantas Joana R. , Silva Karina R. , Souto Débora L. , Pereira Maria de Fátima C. , Moreira Jessica P. , Luiz Ronir R. , Claudio-Da-Silva Cesar S. , Gabbay Monica A. L. , Dib Sergio A. , Couri Carlos E. B. , Maiolino Angelo , Rebelatto Carmen L. K. , Daga Debora R. , Senegaglia Alexandra C. , Brofman Paulo R. S. , Baptista Leandra Santos , Oliveira José E. P. , Zajdenverg Lenita , Rodacki Melanie 

TITLE=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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00993

DOI=10.3389/fimmu.2020.00993

ISSN=1664-3224

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 10<sup>6</sup> 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<sup>+</sup>FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3).</p><p><bold>Results:</bold> 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 (<italic>n</italic> = 8), mild local reactions (<italic>n</italic> = 7), tachycardia (<italic>n</italic> = 4), abdominal cramps (<italic>n</italic> = 1), thrombophlebitis (<italic>n</italic> = 4), mild floaters (<italic>n</italic> = 2), central retinal vein occlusion (<italic>n</italic> = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; <italic>p</italic> = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; <italic>p</italic> = 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; <italic>p</italic> = 0.01). CP variations did not differ between groups (−4.6 ± 29.1% vs. +2.3 ± 59.65%; <italic>p</italic> = 0.83).</p><p><bold>Conclusions:</bold> Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D.</p><p><ext-link ext-link-type="uri" xlink:href="https://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink"><bold>ClinicalTrials.gov registration:</bold></ext-link> NCT03920397.</p>