Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

Abstract

Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 10 6 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/-0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

New therapeutic approaches for type 1 diabetes: Disease-modifying therapies

“…Similar results were obtained in the studies of Araujo et al [ 102 ] and Dantas et al [ 103 ], where a single dose of adipose-derived MSC infusion were combined with daily 2000 IU vitamin D 3 supplementation. Compared to control subjects on traditional treatment, improved HbA 1C levels and reduced insulin doses have been found 3-mo after MSC infusion[ 102 ], while basal C-peptide levels remained the same at first but significantly improved for the 6-mo follow-up measurement[ 102 , 103 ]. It has to be mentioned though that most patients reported transient headache and local reactions, and further mild but resolving adverse events were also reported by a significant amount of the study population.…”

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

“…We have previously reported a comparison between our patients and individuals that used only VIT D supplementation for 6 months and took part in a previous study. The CP AUC could not be compared since this group had only basal e peak CP, but ASC + VIT D had an increase in basal CP and a better HbA1c after 6 months when compared to VIT D supplementation group and controls (59). VIT D can act in lymphocyte proliferation, cellular autoimmune pathways and stimulated T regulatory response (19,20).…”

Stem cell-based therapy for human diseases

“…The use of autologous AT-MSCs in combination with vitamin D was safe and improved HbA1 C levels 6 months post administration. 266 WJ-MSCs were used as the main MSCs for the treatment of new-onset T1DM, which showed a significant improvement in both HbA1 C and C-peptide levels when compared to those of the control group at three and six months post administration. 267 , 268 The combination of allogeneic WJ-MSCs with autologous BM-derived mononuclear cells improved insulin secretion and reduced insulin requirements in patients with T1DM.…”