利用跨胚层共发育类器官芯片生物工程构建心脑共发育体模型

Xuemei Huang ,  Wen Zhao ,  Yuwen Wang ,  Yuxin Wang ,  Tao Chen ,  Lili Zhu ,  Yiran Zhang ,  Jibo Wang ,  Hanwen Cao ,  Yuhang Fan ,  Yunnan Liu ,  Xiaobing Jiang ,  Linlin Bi ,  Changyong Li ,  Pu Chen

工程(英文) ›› 2026, Vol. 62 ›› Issue (7) : 118 -129.

工程(英文) ›› 2026, Vol. 62 ›› Issue (7) : 118 -129. DOI: 10.1016/j.eng.2025.09.022
研究论文

利用跨胚层共发育类器官芯片生物工程构建心脑共发育体模型

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Bioengineering of Heart–Brain Codevelopoid Model Via Trans-Germ-Layer Codevelopment Organoid Chip

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摘要

器官间互作对于器官发生和成熟至关重要,其失调可导致发育障碍。然而,现有生理相关的人源模型在重现早期发育阶段器官间交叉对话方面的能力仍十分有限。本研究开发了一种跨胚层共发育类器官芯片(TGCO-Chip),可在精确控制的生化条件下,使源于共同上游谱系的干细胞聚集体共发育产生两个相互联系但命运不同的类器官。具体而言,具体而言,我们利用该芯片建立了人多能干细胞来源的心脏‑大脑共发育体(HBC)模型,该模型模拟了心脏和大脑的发育特征,包括细胞谱系、组织结构及功能特性。同时,HBC模拟了神经突起向心脏组织的投射及其在器官发生早期对心脏的调控作用。与相互连接的心脏‑心脏类器官相比,神经隔室显著提高了心脏区域的搏动频率和收缩幅度。转录组分析证实,HBC中的神经隔室促进了心脏的分化与成熟。总体而言,TGCO-Chip平台为源于共同祖细胞谱系的多类器官复合体的生物工程构建提供了创新工具。共发育体在发育生物学、疾病建模和再生医学中具有广阔应用前景,并为理解不同细胞谱系与组织间的动态交互提供了全新视角。

Abstract

Interorgan interactions are essential for organogenesis and maturation, with their dysregulation leading to developmental disorders. However, the ability of current physiologically relevant human models to recapitulate interorgan crosstalk during early developmental stages remains limited. Here, we develop a trans-germ-layer codevelopment organoid chip (TGCO-Chip) that enables the coemergence of two interconnected distinct organoids from a common upstream-lineage stem cell aggregate under well-controlled biochemical conditions. Specifically, we established a human pluripotent stem cell-derived heart–brain codevelopoid (HBC) model using a TGCO-Chip, and the codevelopoid recapitulated the developmental features of the heart and brain, including cell lineages, tissue architecture, and functionality. Furthermore, codevelopoids emulate neural projections to cardiac tissues and their regulatory effects during the early developmental stage of organogenesis. Compared with the interconnected heart–heart organoids, the neural compartment significantly increased the average cardiac beating rates and contraction amplitudes. Transcriptomic analysis confirmed that neural compartments in HBCs promoted cardiac differentiation and maturation. Overall, the TGCO-Chip platform provides an innovative tool for bioengineering multiorganoid complexes derived from shared progenitor lineages. Codevelopoids hold immense potential for applications in developmental biology, disease modeling, and regenerative medicine and can provide unprecedented insights into the dynamic interactions between different cell lineages and tissues.

关键词

共发育体 / 多类器官 / 类器官芯片 / 心脑轴 / 器官间互作

Key words

Codevelopoid / Multiorganoid / Organoid chip / Heart–brain axis / Interorgan interaction

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Xuemei Huang,Wen Zhao,Yuwen Wang,Yuxin Wang,Tao Chen,Lili Zhu,Yiran Zhang,Jibo Wang,Hanwen Cao,Yuhang Fan,Yunnan Liu,Xiaobing Jiang,Linlin Bi,Changyong Li,Pu Chen. 利用跨胚层共发育类器官芯片生物工程构建心脑共发育体模型[J]. 工程(英文), 2026, 62(7): 118-129 DOI:10.1016/j.eng.2025.09.022

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