Type 1 Diabetes (T1D) is a highly complex and prevalent metabolic disease caused by dysfunctions of pancreatic islets. Over the past decade, diabetes research and treatments have focused on insulin restoration and glucose homeostasis, especially the regenerative approaches for stem cell based therapies for T1D. Nevertheless, unravelling the islet developmental processes and physiopathology of diabetes requires development of in vitro models that mimic the structure and function of islet of Langerhans.

Organoids have progressively revolutionized three-dimensional cell culture allowing development of more physiologically relevant models that recapitulate cellular interactions and responses more accurately.

Here, we provide insights into advanced islet organoid models focusing on their generation, characteristics, applications, and challenges. We discuss state-of-the-art tissue engineering strategies to recapitulate islet development and pancreatic niche microenvironment by exploring different cell sources of insulin-producing cells, including primary islet cells and cell line aggregation, transdifferentiation from adult somatic cells, and differentiation from stem cells. We discuss the significance of replicating the islet microenvironment through extracellular matrices and scaffolds, as well as vascular and immunomodulatory approaches. We highlight the potential of organ-on-chip technologies to closely recapitulate the complex microenvironment of pancreatic tissues providing platforms for disease modelling, drug screening and regenerative medicine. Despite the challenges, islet organoids combined with microfluidics represent a promising tool for the understanding of T1D pathogenesis and developing innovative therapies.