AG73-GelMA/AlgMA hydrogels provide a stable microenvironment for the generation of pancreatic progenitor organoids

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Patient specific induced pluripotent stem cells (iPSCs) derived β cells represent an effective means for disease modeling and autologous diabetes cell replacement therapy. In this study, an AG73-5%gelatin methacryloyl (GelMA) /2% alginate methacrylate (AlgMA) hydrogel was employed to generate pancreatic progenitor (PP) organoids and improve stem cell-derived β (SC-β) cell differentiation protocol. The laminin-derived homolog AG73, which mimics certain cell‒matrix interactions, facilitates AKT signaling pathway activation to promote PDX1 + /NKX6.1 + PP organoid formation and effectively modulates subsequent epithelial-mesenchymal transition (EMT) in the endocrine lineage. The 5%GelMA/2%AlgMA hydrogel mimics the physiological stiffness of the pancreas, providing the optimal mechanical stress and spatial structure for PP organoid differentiation. The Syndecan-4 (SDC4)-ITGAV complex plays a pivotal role in the early stages of pancreatic development by facilitating the formation of SOX9 + /PDX1 + bipotent PPs. Our findings demonstrate that AG73-GelMA/AlgMA hydrogel-derived SC-β cells exhibit enhanced insulin secretion and accelerated hyperglycemia reversal in vivo. This study presents a cost-effective, stable, and efficient alternative for the comprehensive 3D culture of SC-β cells in vitro by mitigating the uncertainties associated with conventional culture methods.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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