Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial

Abstract

Background Type-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients. Methods After receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation. Results The results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices. Conclusions Taken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes. Trial registration: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308).

Successful lifestyle modifications may underlie umbilical cord-mesenchymal stromal cell effects in type 2 diabetes mellitus

“…Autologous hematopoietic stem cell (AHSC) bone marrow (BM) transplantation (AHSC-BMT) can lead to complete and durable remission in patients with new-onset T1DM[ 15 - 18 ]. Moreover, confirming earlier studies, early autologous MSC transplantation in newly-diagnosed T1DM children is reported as a promising, safe, and effective treatment, significantly improving HbA1c and C-peptide levels and shifting pro-inflammatory cytokines to anti-inflammatory cytokines, ultimately mitigating hypoglycemic episodes[ 19 , 20 ]. In T2DM, Bhansali et al [ 21 , 22 ] showed that autologous BM-MSCs (BM-AMSCs) and autologous BM-mononuclear cells (BM-AMNCs) result in sustained reduction in insulin doses, with improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs[ 21 - 23 ].…”

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

“…HbA 1C , fasting C-peptide and insulin requirement were not significantly different compared to the control group[ 107 ]. In contrast, Izadi et al [ 108 ] found improved HbA 1C and C-peptide levels, a reduced number of hypoglycemic events and increased anti-inflammatory patterns. Furthermore, early BM-MSC transplantation (< 1 year after disease onset) further improved HbA 1C levels and C-peptide levels compared to those who received the transplantation > 1 year after disease onset[ 108 ], similar to that of UC-MSC.…”

Research Progress on Mesenchymal Stem Cells for the Treatment of Diabetes and Its Complications

“…In a randomized, double-blind, phase I/II clinical trial, 11 patients with T1DM were treated with BM-MSCs, and the percentage of HbAc1 was significantly reduced at 12 months. Cytokine interleukin 4 (IL-4) and interleukin 10 (IL-10), which have anti-inflammatory effects, were significantly increased, while tumor necrosis factor-alpha (TNF- α ), which has proinflammatory effects, was significantly decreased [ 10 ]. Taken together, these results showed that the use of MSCs reduced HbAc1 and insulin requirements in T1DM patients, decreased the levels of signature antibodies against GAD and ZnT8 in T1DM patients, increased CP levels, and enhanced systemic anti-inflammatory capacity.…”