A Preliminary Safety and Efficacy Evaluation of Direct Intra-pancreatic Tail Delivery of Autologous Bone Marrow-Derived Mononuclear Cells in Egyptian Patients with Type 1 Diabetes Mellitus

Abstract

Background: Type 1 diabetes (T1D) results from the autoimmune destruction of islet s-cells. Recent studies have shown that cell therapy shows promise in combating this. However, many problems are associated with the systemic administration of these cells, including nonspecific accumulation of cells in an organ other than the target organ. The objective of this study was to evaluate the safety and efficacy of autologous bone marrow-derived mononuclear cells (A-BMMNCs) via Direct Trans-gastric Intra-pancreatic (DTI) delivery as a potential treatment for Egyptian patients with T1D. Methods: 17 patients whose ages ranged between 2 and 30 years were assigned to receive a single administration of A-BMMNCs via DTI delivery and followed up for 1 year. The main outcome was assessment of safety. We also assessed islet cells and insulin antibodies pre-transplantation and, in patients who were serologically positive for these, again 6 months post-transplantation. Glycated hemoglobin (HbA1c) and fasting and 2 h postprandial C-peptide levels (FCP, 2h-CP) were also measured to evaluate s-cell function. Finally, we determined insulin doses. Results: No complications were recorded during the study across all patients. Islet cell antibodies were undetectable pre-transplantation for all patients. 10/17 patients were positive for anti-insulin antibodies pretransplantation and 7/17 were negative; of those who were positive, 6 converted to being negative for anti-insulin antibodies and 4 were still positive for anti-insulin antibodies) within 1 year post-transplantation. HbA1c and insulin doses were significantly lower at 5 months post-transplantation compared with baseline. FCP levels rose significantly in the first 2 months with little change in 2h-CP levels. Conclusions: A-BMMNCs transplantation via DTI delivery route is a simple, safe and innovative procedure. It can temporarily modify the course of T1D, could be a beneficial treatment modality in the future to control the progression of the disease and potentially opening a new way to cure diabetes (ISRCTN15591075).