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通过生物工程释放人类多能干细胞来源的肾脏类器官的全部潜能。

Unlocking the full potential of human pluripotent stem cell-derived kidney organoids through bioengineering.

作者信息

Goux Corredera Iphigénie, Amato Gaia, Moya-Rull Daniel, Garreta Elena, Montserrat Nuria

机构信息

Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.

Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.

出版信息

Kidney Int. 2025 Jul;108(1):38-47. doi: 10.1016/j.kint.2025.01.043. Epub 2025 Apr 23.

DOI:10.1016/j.kint.2025.01.043
PMID:40280411
Abstract

Human pluripotent stem cells hold inherent properties, allowing researchers to recapitulate key morphogenetic processes. These characteristics, coupled with bioengineering techniques, have led to the definition of early procedures to derive organ-like cell cultures, the so-called organoids. With regard to kidney organoids, challenges stand ahead, such as the need to enhance cellular composition, maturation, and function to that found in the native organ. To this end, the kidney organoid field has begun to nourish from innovative engineering approaches aiming to gain control on the externally imposed biochemical and biophysical cues. In this review, we first introduce how previous research in kidney development and human pluripotent stem cells has informed the establishment of current kidney organoid procedures. We then discuss recent engineering approaches to guide kidney organoid self-organization, differentiation, and maturation. In addition, we present current strategies to engineer vascularization and promote in vivo-like physiological microenvironments as potential solutions to increase kidney organoid lifespan and functionality. We finally emphasize how working at the cusp of cell mechanics and computational biology will set the ground for successful translational applications of kidney organoids.

摘要

人类多能干细胞具有内在特性,使研究人员能够重现关键的形态发生过程。这些特性与生物工程技术相结合,促成了早期获取类器官细胞培养物(即所谓的类器官)程序的定义。就肾脏类器官而言,仍面临诸多挑战,比如需要将细胞组成、成熟度和功能提升至天然器官的水平。为此,肾脏类器官领域已开始借助创新工程方法,旨在控制外部施加的生化和生物物理信号。在本综述中,我们首先介绍以往在肾脏发育和人类多能干细胞方面的研究如何为当前肾脏类器官程序的建立提供了依据。然后,我们讨论最近用于指导肾脏类器官自我组织、分化和成熟的工程方法。此外,我们介绍了目前构建血管化和促进类体内生理微环境的策略,作为延长肾脏类器官寿命和增强其功能的潜在解决方案。我们最后强调,在细胞力学和计算生物学的交叉领域开展研究将为肾脏类器官的成功转化应用奠定基础。

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