Generation of Bone Marrow Mesenchymal Stem Cell-Derived Islet Organoid-like Structures From Fresh Pancreatic Tissue

As a prevalent chronic illness across the globe, diabetes mellitus (DM) is marked by disrupted glucose balance in the body. In type 1 diabetes mellitus (T1DM), autoimmune responses destroy pancreatic β-cells entirely, resulting in total insulin insufficiency. Patients with this condition need lifelong supplemental insulin treatment. The present study intends to create a reliable and economical culture platform to generate pancreatic islet organoid-like structures from bone marrow mesenchymal stem cells (BMSCs). This platform can not only ease the shortage of donor islets for transplantation, but also serve as an in vitro model for diabetes-related research. By optimizing the preparation process of porcine pancreatic tissue lysate (centrifugation at 12,000 rpm for 30 min at 4 °C, followed by 0.22 µm filtration for sterilization), BMSCs were successfully induced to differentiate into pancreatic islet organoid-like structures. Morphological validation confirmed that only induced BMSCs formed compact, plump, and highly transparent islet-like aggregates, whereas noninduced BMSCs exhibited significant vacuolization and reduced transparency. Dynamic monitoring showed that cell aggregates (50-100 µm in diameter) formed on day 16 of culture and developed into capsule- like structures (200-300 µm in diameter) by day 22. This method is simple to operate, cost- effective, and does not require complex equipment. The resulting organoids are morphologically similar to pancreatic islets, providing a tool for in vitro studies and related drug screening.