美国印第安纳大学郭峰研究小组发现血管网络激发的可扩散支架工程功能中脑类器官。相关论文于2025年3月17日发表于国际顶尖学术期刊《细胞—干细胞》杂志上。

在此，该研究组提出了血管网络启发的可分化（VID）支架来模拟生理分化物理，以产生功能性类器官并对其药物反应进行表型分析。具体来说，VID支架，3D打印网状管状通道网络，成功地在普通主题孔板中设计了几乎没有坏死和缺氧的人类中脑类器官。与传统类器官相比，这些工程类器官具有更多与生理相关的特征和功能，包括中脑特异性身份、氧代谢、神经元成熟和网络活动。

此外，与具有显著扩散限制的传统类器官相比，这些工程类器官也更好地概括了芬太尼暴露后的药理反应，例如神经活动的变化。这个平台可能为类器官的发展和治疗创新提供见解。

据悉，类器官，来源于干细胞的三维器官样组织培养物，在发育生物学、药物发现和再生医学方面显示出有希望的潜力。然而，目前的类器官，特别是神经类器官的功能和表型仍然受到氧气、营养物质、代谢物、信号分子和药物分化不足的限制。

附：英文原文

Title: Vascular network-inspired diffusible scaffolds for engineering functional midbrain organoids

Author: Hongwei Cai, Chunhui Tian, Lei Chen, Yang Yang, Alfred Xuyang Sun, Kyle McCracken, Jason Tchieu, Mingxia Gu, Ken Mackie, Feng Guo

Issue&Volume: 2025-03-17

Abstract: Organoids, 3D organ-like tissue cultures derived from stem cells, show promising potential for developmental biology, drug discovery, and regenerative medicine. However, the function and phenotype of current organoids, especially neural organoids, are still limited by insufficient diffusion of oxygen, nutrients, metabolites, signaling molecules, and drugs. Herein, we present vascular network-inspired diffusible (VID) scaffolds to mimic physiological diffusion physics for generating functional organoids and phenotyping their drug response. Specifically, the VID scaffolds, 3D-printed meshed tubular channel networks, successfully engineer human midbrain organoids almost without necrosis and hypoxia in commonly used well plates. Compared with conventional organoids, these engineered organoids develop more physiologically relevant features and functions, including midbrain-specific identity, oxygen metabolism, neuronal maturation, and network activity. Moreover, these engineered organoids also better recapitulate pharmacological responses, such as neural activity changes to fentanyl exposure, compared with conventional organoids with significant diffusion limits. This platform may provide insights for organoid development and therapeutic innovation.

DOI: 10.1016/j.stem.2025.02.010

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00049-9