Abstract：
Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump-less recirculating organ-on-chip platform that combines human pluripotent stem cell (sc)-derived sc-liver and sc-islet organoids is presented. The platform reproduces key aspects of the metabolic cross-talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc-islet and sc-liver organoids while preserving a reduced release of pro-inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc-liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc-islets produce pro-inflammatory cytokines on-chip. Finally, the platform reproduces known effects of anti-diabetic drugs on-chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on-chip, as well as for testing potential therapeutic interventions.
摘要：
2型糖尿病(T2DM),肥胖，和代谢功能障碍相关的脂肪变性肝病（MASLD）是流行病学相关的疾病，在全球范围内患病率不断上升。虽然导致这些疾病发作和发展的机制尚未完全了解，用于研究调节能量代谢的中央器官之间的协调相互作用的预测性组织表示，尤其是肝脏和胰岛，是需要的。这里,提出了一种双无泵再循环芯片上器官（dual-rOoC）平台，该平台结合了人类多能干细胞（sc）来源的sc-肝脏和sc-胰岛类器官。该平台再现了两个器官之间代谢串扰的关键方面，包括葡萄糖水平和选定的激素，并支持sc-胰岛和sc-肝脏类器官的活力和功能，同时保留促炎细胞因子的减少释放。在对高脂和果糖治疗的代谢破坏模型中，sc-肝类器官表现出脂肪变性和胰岛素抵抗的标志，而sc-胰岛在芯片上产生促炎细胞因子。最后,该平台在芯片上再现抗糖尿病药物的已知作用。一起来看,该平台为肥胖的功能研究提供了基础，T2DM,和芯片上的MASLD，以及测试潜在的治疗干预措施。本文受版权保护。保留所有权利。
