Mesenchymal Stem Cells Transplantation in newly diagnosed type-1 diabetes patients:a phase I/II Randomized Controlled trial

Abstract

Background & Aim Background Insulin injection is a routine treatment for type-1 diabetes which couldn't result in physiologic reaction to blood glucose changes and patients are encountered with diabetes complications. Therefore, a treatment option that leads to modulate the immune system and mitigate the procedure of insulitis could be a hopeful clinical choice. Mesenchymal Stem Cells (MSC) have been shown to have immunomodulatory and regenerative effects. Aim In this clinical trial, autologous bone marrow-derived MSCs (BM-MSCs) were used for immune response modulation and to assess the safety and efficacy of transplantation in newly diagnosed type-1 diabetes patients. Methods, Results & Conclusion Methods A Crossover triple blinded randomized controlled trial in two 12-months periods conducted between 2015 and 2020, at “Royan Institute” with the collaboration of “Growth and Development Research Center of Tehran University of Medical Sciences” in Tehran, Iran. Patients of 8 to 40 years old who have been diagnosed with type-1 diabetes in no more than 6weeks, and met other inclusion criteria, were randomly assigned to receive either two doses of 1 million per kg of patient's body weight MSCs or placebo. Safety was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Efficacy was defined as a reduction in the number of hypoglycemic episodes and changes in metabolic indices compared to baseline. Patients’ Quality of life (QOL) was assessed by SF36 and Diabetes Specific QOL (DSQOL) Questionnaires. Percent of regulatory T cells population were assessed in patients’ blood before and 48 hours after MSCs transplantation by flow cytometry. Statistical analysis was done by SPSS v.13. Results The primary outcome was safety concluding there were not any major adverse events in this trial. The total number of hypoglycemic episodes was significantly reduced in patients who received MSCs compared to the placebo group. There were not any significant differences in metabolic indices between intervention and placebo groups. DSQOL showed a significant increase in QOL of patients received MSCs after 12 months compared to baseline. SF36 showed a considerable increase in QOL in patients received MSC. The population of regulatory T cells in patients’ blood was significantly increased 48 hours after MSC transplantation compared to baseline. Conclusion Autologous transplantation of BM- MSCs in newly diagnosed type-1 diabetes patients is safe, feasible, and could improve some of the clinical parameters.