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治疗开发的进展:肾脏类器官和芯片器官。

Advancements in therapeutic development: kidney organoids and organs on a chip.

机构信息

Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Centre de Recherche des Cordeliers, INSERM, EMR 8228, Paris, France.

Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.

出版信息

Kidney Int. 2024 Apr;105(4):702-708. doi: 10.1016/j.kint.2023.11.035. Epub 2024 Jan 29.

Abstract

The use of animal models in therapeutic development has long been the standard practice. However, ethical concerns and the inherent species differences have prompted a reevaluation of the experimental approach in human disease studies. The urgent need for alternative model systems that better mimic human pathophysiology has led to the emergence of organoids, innovative in vitro models, to simulate human organs in vitro. These organoids have gained widespread acceptance in disease models and drug development research. In this mini review, we explore the recent strides made in kidney organoid differentiation and highlight the synergistic potential of incorporating organ-on-chip systems. The emergent use of microfluidic devices reveals the importance of fluid flow in the maturation of kidney organoids and helps decipher pathomechanisms in kidney diseases. Recent research has uncovered their potential applications across a wide spectrum of kidney research areas, including hemodynamic forces at stake in kidney health and disease, immune cell infiltration, or drug delivery and toxicity. This convergence of cutting-edge technologies not only holds promise for expediting therapeutic development but also reflects an acknowledgment of the need to embrace innovative and more human-centric research models.

摘要

在治疗开发中使用动物模型一直是标准做法。然而,出于伦理方面的考虑以及物种间固有的差异,促使人们重新评估人类疾病研究中的实验方法。因此,迫切需要能够更好地模拟人类病理生理学的替代模型系统,这导致了类器官的出现,即创新性的体外模型,用于在体外模拟人体器官。这些类器官在疾病模型和药物开发研究中得到了广泛认可。在这篇小型综述中,我们探讨了肾脏类器官分化方面的最新进展,并强调了将器官芯片系统纳入的协同潜力。微流控设备的新兴应用揭示了在肾脏类器官成熟过程中流体流动的重要性,并有助于阐明肾脏疾病中的病理机制。最近的研究揭示了它们在广泛的肾脏研究领域中的潜在应用,包括肾脏健康和疾病中涉及的血流动力学、免疫细胞浸润或药物输送和毒性。这些尖端技术的融合不仅有望加速治疗开发,而且还反映出人们认识到需要采用创新的、更以人为本的研究模型。

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