Mao Yihuan, Wang Siqi, Yu Jiazhen, Li Wei
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Key Laboratory of Organ Regeneration and Reconstruction, Chinese Academy of Sciences, Beijing, China.
Med Rev (2021). 2024 Mar 8;4(2):90-109. doi: 10.1515/mr-2023-0050. eCollection 2024 Apr.
Pluripotent stem cells (PSCs), characterized by self-renewal and capacity of differentiating into three germ layers, are the programmable building blocks of life. PSC-derived cells and multicellular systems, particularly organoids, exhibit great potential for regenerative medicine. However, this field is still in its infancy, partly due to limited strategies to robustly and precisely control stem cell behaviors, which are tightly regulated by inner gene regulatory networks in response to stimuli from the extracellular environment. Synthetic receptors and genetic circuits are powerful tools to customize the cellular sense-and-response process, suggesting their underlying roles in precise control of cell fate decision and function reconstruction. Herein, we review the progress and challenges needed to be overcome in the fields of PSC-based cell therapy and multicellular system generation, respectively. Furthermore, we summarize several well-established synthetic biology tools and their applications in PSC engineering. Finally, we highlight the challenges and perspectives of harnessing synthetic biology to PSC engineering for regenerative medicine.
多能干细胞（PSCs）具有自我更新和分化为三个胚层的能力，是生命的可编程构建模块。PSCs衍生的细胞和多细胞系统，特别是类器官，在再生医学中展现出巨大潜力。然而，该领域仍处于起步阶段，部分原因是用于稳健且精确控制干细胞行为的策略有限，而干细胞行为受内部基因调控网络严格调控，以响应细胞外环境的刺激。合成受体和基因回路是定制细胞感知与反应过程的强大工具，表明它们在精确控制细胞命运决定和功能重建中具有潜在作用。在此，我们分别综述了基于PSCs的细胞治疗和多细胞系统生成领域取得的进展以及需要克服的挑战。此外，我们总结了几种成熟的合成生物学工具及其在PSCs工程中的应用。最后，我们强调了利用合成生物学进行PSCs工程以实现再生医学所面临的挑战和前景。
