在三维静态和动态悬浮条件下,从hESCs大规模生产可扩增的肝母细胞类器官和极化肝细胞类器官。

IF 5.9 1区 生物学 Q2 CELL BIOLOGY
Haibin Wu, Jue Wang, Shoupei Liu, Yiyu Wang, Xianglian Tang, Jinghe Xie, Ning Wang, Huanhuan Shan, Sen Chen, Xueyan Zhang, Weiping Zeng, Chuxin Chen, Yinjie Fu, Liangxue Lai, Yuyou Duan
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引用次数: 0

摘要

迄今为止,大规模地产生有活力和功能的肝细胞仍然是一个挑战。在低浓度基质的支持下,采用三维悬浮条件,开发了一种新的培养系统,可以在培养皿和生物反应器中从人胚胎干细胞(hESCs)中产生可扩展的肝母细胞类器官(HB-orgs)和成熟的极化肝细胞类器官(P-hep-orgs)。使用scRNA-seq和功能分析来表征HB-orgs和P-hep-orgs。hesc衍生的HB-orgs至少可增殖15代,4周内可增殖1012个细胞。从HB-orgs分化而来的P-hep-orgs表现出成熟肝细胞的极化特征。此外,单细胞RNA测序显示,P-hep-orgs中超过40%的细胞与人原代肝细胞高度保真。最终,在生物反应器中,大量扩增的HB-orgs可在1周内产生数量相近的P-hep-orgs,这是由于能量代谢的增强促进了HB-orgs的扩增和P-hep-orgs的成熟。通过提供一个具有成本效益和强大的平台,我们的研究代表了制造大规模功能hesc衍生肝细胞的重要一步,用于基于细胞的治疗、疾病建模、药理学和毒理学研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Large-Scale Production of Expandable Hepatoblast Organoids and Polarised Hepatocyte Organoids From hESCs Under 3D Static and Dynamic Suspension Conditions.

To date, generating viable and functional hepatocytes in large scale remains challenge. By employing 3D suspension condition with the support of low concentration Matrigel, a novel culture system was developed to generate expandable hepatoblast organoids (HB-orgs) and mature polarised hepatocyte organoids (P-hep-orgs) from human embryonic stem cells (hESCs) in both dishes and bioreactors. scRNA-seq and functional assays were used to characterise HB-orgs and P-hep-orgs. hESC-derived HB-orgs could proliferate at least for 15 passages, leading to 1012 in total cells in 4 weeks. P-hep-orgs differentiated from HB-orgs displayed characteristics of mature hepatocytes with polarisation. Moreover, single-cell RNA sequencing exhibited that over 40% of cells in P-hep-orgs were highly fidelity with human primary hepatocytes. Eventually, large-scale production of P-hep-orgs could be generated from massively expanded HB-orgs within 1 week with similar number in bioreactors, which were achieved by the enhancements in energy metabolism contribute to the expansion of HB-orgs and maturation of P-hep-orgs in bioreactors. By providing a cost-efficient and robust platform, our study represents a significant step toward manufacturing large-scale functioning hESC-derived hepatocytes for cell-based therapeutics, disease modelling, pharmacology and toxicology studies.

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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
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