Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on β-cell function and insulin sensitivity

摘要

BackgroundInsulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. MethodsSeven T2DM patients with the duration of disease?≥5?years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4?IU per kg per day) and HbA1c?≤?7.5% (≤58.0?mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by?≥50% from baseline, while maintaining HbA1c ResultsSix out of 7 (90%) patients achieved the primary end-point. At 6?months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p ConclusionABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM. Trial registration - Clinicaltrials.gov NCT01759823