Kim Myungji, Cho Seungyeun, Hwang Dong Gyu, Shim In Kyong, Kim Song Cheol, Jang Jiwon, Jang Jinah
Division of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Center for 3D Organ Printing and Stem Cells, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Nat Commun. 2025 Feb 7;16(1):1430. doi: 10.1038/s41467-025-56665-5.
Pancreatic islets are densely packed cellular aggregates containing various hormonal cell types essential for blood glucose regulation. Interactions among these cells markedly affect the glucoregulatory functions of islets along with the surrounding niche and pancreatic tissue-specific geometrical organization. However, stem cell (SC)-derived islets generated in vitro often lack the three-dimensional extracellular microenvironment and peri-vasculature, which leads to the immaturity of SC-derived islets, reducing their ability to detect glucose fluctuations and insulin release. Here, we bioengineer the in vivo-like pancreatic niches by optimizing the combination of pancreatic tissue-specific extracellular matrix and basement membrane proteins and utilizing bioprinting-based geometrical guidance to recreate the spatial pattern of islet peripheries. The bioprinted islet-specific niche promotes coordinated interactions between islets and vasculature, supporting structural and functional features resembling native islets. Our strategy not only improves SC-derived islet functionality but also offers significant potential for advancing research on islet development, maturation, and diabetic disease modeling, with future implications for translational applications.
胰岛是紧密堆积的细胞聚集体，包含对血糖调节至关重要的各种激素细胞类型。这些细胞之间的相互作用以及周围的微环境和胰腺组织特异性几何结构显著影响胰岛的糖调节功能。然而，体外生成的干细胞衍生胰岛通常缺乏三维细胞外微环境和周血管系统，这导致干细胞衍生胰岛不成熟，降低了它们检测葡萄糖波动和释放胰岛素的能力。在此，我们通过优化胰腺组织特异性细胞外基质和基底膜蛋白的组合，并利用基于生物打印的几何引导来重建胰岛周边的空间模式，对体内样胰腺微环境进行生物工程改造。生物打印的胰岛特异性微环境促进了胰岛与血管之间的协调相互作用，支持了类似于天然胰岛的结构和功能特征。我们的策略不仅改善了干细胞衍生胰岛的功能，还为推进胰岛发育、成熟和糖尿病疾病建模的研究提供了巨大潜力，对转化应用具有未来意义。
