Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus

• Islet organoids derived from stem cells offer a promising alternative to donor islets for transplantation, potentially overcoming donor shortages and immune rejection issues. • Current islet organoid models have limitations in composition, structure, and function compared to native islets, necessitating further optimization of differentiation protocols and 3D biomimetic materials. • The review highlights the need for multi-tissue organoid systems to better mimic in vivo conditions and improve insulin secretion functionality. • Safety concerns such as tumorigenicity, immune rejection, infection, and thrombosis must be addressed before clinical translation of islet organoid transplantation.