Adipose tissue-derived stromal/stem cells transplantation + cholecalciferol in recent-onset type 1 diabetes patients: twelve months follow up.

Abstract:OBJECTIVE: To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation+cholecalciferol(VITD) in patients with recent-onset type 1 diabetes (T1D).METHODS: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs(1Kgx10⁶ cells) and VITD 2000UI/day for 12 months(group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve(CPAUC), insulin dose, HbA1c and frequency of CD4⁺FoxP3⁺ T-cells(flow cytometry)were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12).RESULTS: 11 patients completed the 12 months follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24+/-0.18vs0.53+/-0.23UI/kg,p=0.04), T6(0.24+/-0.15vs0.66 +/- 0.33 UI/kg,p=0.04) and T12(0.39+/-0.15vs0.74+/-0.29 UI/Kg,p=0.04).HbA1c was lower at T6(6.7+/-0.79vs8.75+/-0.95%,p=0.01), without significant differences at T12(7.3+/-1.11% in group 1vs8.90+/-1.33 in group 2,p=0.16).CPAUC was not significantly different at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23).Six patients (85,7%) in group 1 were in partial clinical remission(CR) at T6 vs none in group 2,p=0.01,4 remained in remission until 12 months. Patients with partial CR exhibited higher FOX P3 expression in CD4⁺lymphocytes at T6 and T12(p=0.004 and p=0.02, respectively).VITD levels were higher in patients that underwent partial CR at T6. One patient has a recurrence of a benign teratoma that was surgically removed, not associated to the intervention was observed in a patient from group 1.CONCLUSIONS: ASCs+VITD without immunosuppression was safe and associated lower insulin requirements, a better glycemic control and a transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained. Trial registration : ClinicalTrial.gov NCT03920397