合成生物学 ›› 2024, Vol. 5 ›› Issue (4): 734-753.DOI: 10.12211/2096-8280.2023-100

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干细胞模拟发育:细胞元件、胚胎模型与工程方法

韩宜钊, 郭佳, 邵玥   

  1. 清华大学航天航空学院工程力学系,生物力学与医学工程研究所,北京 100084
  • 收稿日期:2023-12-01 修回日期:2024-03-04 出版日期:2024-08-31 发布日期:2024-09-19
  • 通讯作者: 邵玥
  • 作者简介:韩宜钊(1997—),女,博士研究生。研究方向为基于生物工程的干细胞发育生物学。E-mail:hanyz22@mails.tsinghua.edu.cn
    邵玥(1986—),男,副教授,博士生导师,“国家海外高层次青年人才引进计划”获得者。研究方向包括生物力学、器官修复、生殖健康、合成胚胎学等。E-mail:yshao@tsinghua.edu.cn
  • 基金资助:
    国家自然科学基金(12102229)

Stem cell-based synthetic development: cellular components, embryonic models, and engineering approaches

Yizhao HAN, Jia GUO, Yue SHAO   

  1. Institute of Biomechanics and Medical Engineering,Department of Engineering Mechanics,School of Aerospace Engineering,Tsinghua University,Beijing 100084,China
  • Received:2023-12-01 Revised:2024-03-04 Online:2024-08-31 Published:2024-09-19
  • Contact: Yue SHAO

摘要:

近百年来,胚胎发育的理论基础主要源于对模式动物的研究,珍稀哺乳动物的发育研究一直受到种间差异、伦理及技术手段等条件的制约。随着干细胞技术的迅猛发展,研究者们利用干细胞构建体外胚胎模型突破传统发育研究的局限性。目前,胚胎模型是否能够完全模拟真实胚胎的发育过程尚待验证,但这无疑为发育生物学研究带来新的可能性。本文以小鼠和人为主要讨论模型,总结用于构建胚胎模型的干细胞种类,阐释不同干细胞在模拟发育过程中的作用和重要性。文章系统呈现了胚胎在不同发育阶段的关键事件和时空动态过程,全面阐述胚胎模型取得的显著成果,详细探讨如何评估胚胎模型的仿生度,以及生物工程学方法在胚胎模型开发中的关键作用,为胚胎模型的进一步优化和发展提供参考。通过对胚胎模型领域的深入研究,有助于更全面细致地了解胚胎发育过程,并为早期发育研究、疾病研究、药物筛选、生殖医学及毒性评估等领域提供更为精确的理论依据和应用工具,进而为未来生命科学的发展开辟新的途径。

关键词: 干细胞, 胚胎模型, 哺乳动物胚胎学, 微环境, 生物工程, 高保真度, 自组装

Abstract:

Over the past century, the scientific foundation of embryonic development has primarily relied upon meticulous examination of developmental processes in model organisms. However, investigating the development of mammals has presented numerous challenges, including interspecies disparities, ethical considerations, and technical constraints. With the rapid advancement of stem cell technology, researchers have endeavored to overcome these obstacles by harnessing the potential of stem cells to generate sophisticated invitro embryo models. The rapid advancement of stem cell technology has revolutionized our approach to study embryonic development. While the ability of current embryo models to fully simulate the authentic developmental process is yet to be verified, they undeniably present new possibilities for developmental biology research. This review primarily focuses on mouse and human, summarizing the types of stem cells used in constructing embryo models and elucidating the roles and importance of different stem cells in simulating developmental processes. This review systematically presents and dissects crucial events and spatiotemporal dynamics in the embryonic development of both mice and humans across various stages. We thoroughly discuss the remarkable milestones achieved by existing embryo models, explore methods for evaluating the biomimicry of these models, and highlight the crucial role of bioengineering methods in embryo model development. The pivotal role of bioengineering in advancing embryonic model development is underscored, emphasizing its indispensable contribution to providing the requisite technical scaffolding for the realization of instruct multicellular induced self-organization with high-level spatiotemporal orders. Additionally, we provide perspectives for the optimization and progressive refinement of embryo models, so as to improve their relevance and applicability. In summary, engineered advances in stem cell-based synthetic development could not only improve our understanding of the inherent complexities of embryos, but also hold the potential for applications in disease research, drug screening, reproductive medicine, toxicological assessments, and other related fields, thereby opening new avenues for both fundamental and translational research.

Key words: stem cells, embryo models, mammalian embryology, microenvironment, bioengineering, high-fidelity, self-organization

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