Hong SoonGweon, Song Minsun, Miyoshi Tomoya, Morizane Ryuji, Bonventre Joseph V, Lee Luke P
Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
bioRxiv. 2024 Oct 29:2024.10.27.620552. doi: 10.1101/2024.10.27.620552.
Kidney organoids, replicating human development, pathology, and drug responses, are a promising model for advancing bioscience and pharmaceutical innovation. However, reproducibility, accuracy, and quantification challenges hinder their broader utility for advanced biological and pharmaceutical applications. Herein, we present a dynamic kidney organoid microphysiological analysis platform (MAP), designed to enhance organoid modeling and assays within physiologically relevant environments, thereby expanding their utility in advancing kidney physiology and pathology research. First, precise control of the dynamic microenvironment in MAP enhances the ability to fine-tune nephrogenic intricacies, facilitating high-throughput and reproducible human kidney organoid development. Also, MAP's miniaturization of kidney organoids significantly advances pharmaceutical research by allowing for detailed analysis of entire nephron segments, which is crucial for assessing the nephrotoxicity and safety of drugs. Furthermore, the MAP's application in disease modeling faithfully recapitulates pathological development and functions as a valuable testbed for therapeutic exploration in polycystic kidney diseases. We envision the kidney organoid MAP enhancing pharmaceutical research, standardizing processes, and improving analytics, thereby elevating the quality and utility of organoids in biology, pharmacology, precision medicine, and education.
肾脏类器官能够复制人类发育、病理和药物反应,是推动生物科学和药物创新的一种很有前景的模型。然而,可重复性、准确性和定量方面的挑战阻碍了它们在先进生物学和药物应用中的更广泛应用。在此,我们展示了一个动态肾脏类器官微生理分析平台(MAP),其设计目的是在生理相关环境中增强类器官建模和检测,从而扩大它们在推进肾脏生理学和病理学研究中的应用。首先,MAP中对动态微环境的精确控制增强了微调肾发生复杂性的能力,促进了高通量和可重复的人类肾脏类器官发育。此外,MAP对肾脏类器官的小型化通过允许对整个肾单位节段进行详细分析,显著推进了药物研究,这对于评估药物的肾毒性和安全性至关重要。此外,MAP在疾病建模中的应用忠实地再现了病理发展,并作为多囊肾病治疗探索的一个有价值的试验台。我们设想肾脏类器官MAP将促进药物研究、规范流程并改进分析方法,从而提高类器官在生物学、药理学、精准医学和教育中的质量和效用。