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Abstract Type I diabetes mellitus (TIDM) is considered one of the most common metabolic disorders affecting all age groups starting mainly in childhood. The main etiology is of unknown origin; however, it may be due to viral infection or autoimmune disorders. It is characterized by insulin insufficiency which results from pancreatic β-islets cells destruction. Many different treatment strategies were used for TIDM treatment, as insulin injection and organ transplantation (whole pancreas or islets transplantation) however due to their drawbacks as painful injections and limitation of organ donor, new lines of treatment have emerged for TIDM. Stem cells could differentiate into insulin producing cells that can physiologically mimic pancreatic islets β-cells and secrete insulin in response to hyperglycemia. Mesenchymal stem cells (MSCs) have shown higher potential and effectiveness in TIDM treatment. Bone marrow is considered one of the common sources of MSCs. Bone marrow mesenchymal stem cells (BM-MSCs) can secrete a variety of immunoregulatory factors in a paracrine manner that impact the ability of innate and acquired immune cells, as well as, autologous and allogeneic immune cells, to perform their immunological functions. However, stem cell transplantation for TIDM presents challenges such as high tumorigenicity risk, unsafety, and low MSC engraftment rate |