Department of Bioengineering, University of California, Berkeley, Berkeley, CA, 94720, USA.
Berkeley Sensor and Actuator Center, University of California, Berkeley, Berkeley, CA, 94720, USA.
Adv Healthc Mater. 2018 Jan;7(2). doi: 10.1002/adhm.201701111. Epub 2017 Dec 28.
The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic β-cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic β-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold-free formation of densely packed β-cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the β-cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the β-cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species-induced caspase-mediated pathway. The β-cells' MAP might provide a potential new map in the pathophysiological mechanisms of β cells.
糖尿病的特征是胰岛素分泌不足和胰高血糖素失调。了解胰岛中胰岛素、胰高血糖素和其他激素的释放机制至关重要。尽管在糖尿病研究和实践方面取得了显著进展，但仍缺乏能够测量胰腺β细胞功能的强大且可重复的模型。本文报道了一种微生理分析平台（MAP），该平台允许胰岛的胰腺β细胞进行均匀的 3D 球体形成、大规模形态表型分析以及慢性血糖和血脂发展的基因表达图谱绘制。MAP 实现了无支架的密集β细胞球体的形成（即，由受生理相关微环境启发的灌注流网络包围的 110 个生物反应器的多个阵列）。MAP 允许对β细胞球体进行动态干扰，并精确控制血糖和血脂，这使我们能够确认高血糖和高血脂条件下β细胞球体中的细胞凋亡主要依赖于活性氧诱导的半胱天冬酶介导途径。该 MAP 可能为β细胞的病理生理学机制提供一个潜在的新图谱。
