Mesenchymal Stromal Cell-Based Immunotherapy for Type 1 Diabetes: From Bench to Bedside

Type 1 diabetes mellitus (T1D) is an autoimmune disease driven by a complex interplay between genetic susceptibility, environmental factors, and dysregulated immune re-sponses, ultimately leading to the progressive destruction of insulin-producing pancre-atic β-cells. Despite substantial advances in glucose monitoring and insulin delivery technologies, current treatment strategies cannot fully reproduce the physiological regu-lation of insulin secretion and do not directly target the underlying autoimmune process. Consequently, increasing attention has been directed toward immunomodulatory ap-proaches aimed at preserving residual β-cell function and modifying disease progres-sion. Mesenchymal stromal cells (MSCs) have emerged as a promising cell-based thera-peutic approach owing to their broad immunomodulatory, anti-inflammatory, and paracrine properties. Importantly, unlike therapies directed predominantly at individual immune targets or pathways, MSCs can simultaneously modulate multiple intercon-nected mechanisms involved in T1D immunopathogenesis, affecting both innate and adaptive immune responses, inflammatory signaling, antigen presentation, and immune tolerance. This broad and multifaceted mode of action provides a strong rationale for in-vestigating MSCs as a therapeutic strategy capable of addressing the complex and highly interconnected nature of T1D autoimmunity. This review examines the major mecha-nisms underlying T1D immunopathogenesis and the multifaceted immunomodulatory effects of MSCs, followed by a critical evaluation of the available preclinical and clinical evidence on MSC-based therapy. The potential of MSCs to preserve β-cell function, mod-ulate immune responses, and improve metabolic outcomes is considered, together with current limitations and challenges for clinical translation.