多囊肾药物筛选模型新进展: 从细胞、动物到类器官

New advances in drug screening models for polycystic kidney disease: from cells and animals to organoids

摘要

多囊肾(polycystic kidney disease, PKD)是一种常见的遗传性肾脏疾病,其特征是肾小管囊肿的异常增生和扩张,最终可引发肾功能衰竭。药物筛选在PKD治疗研究中占据关键地位,但传统的细胞模型和动物模型在模拟疾病复杂性及筛选效率方面存在明显局限,难以满足临床需求。近年来,类器官模型作为创新型体外研究工具,凭借对PKD三维结构、病理特征及患者特异性的精准模拟能力,展现出独特优势与巨大应用潜力。本文系统综述了 PKD药物筛选模型的研究现状,涵盖细胞模型、动物模型、类器官模型以及器官芯片等前沿技术的构建与应用。通过典型案例分析与多模型对比,深入剖析不同模型的特性,明确指出类器官模型在高通量药物筛选、精准医学实践和个性化治疗探索中的核心价值。研究证实,类器官模型能够有效弥补传统模型的不足,有望成为推动PKD治疗研究突破的关键工具,为临床转化开辟全新路径。同时,本文对类器官模型在PKD研究领域的未来发展方向进行了科学展望,以期为后续研究提供参考与启发。

Abstract

Polycystic kidney disease (PKD) is a common hereditary renal disorder characterized by abnormal proliferation and dilation of renal tubular cysts, which can eventually lead to renal failure. Currently, drug screening plays a pivotal role in PKD therapeutic research, but traditional cell and animal models exhibit significant limitations in mimicking disease complexity and screening efficiency, failing to meet clinical needs. In recent years, organoid models, as innovative in vitro research tools, have demonstrated unique advantages and enormous application potential by precisely simulating the three-dimensional structure, pathological features, and patient-specific characteristics of PKD. This article systematically reviewed the research status of PKD drug screening models, covering the construction and application of cell models, animal models, organoid models, and cutting-edge technologies such as organ-on-a-chip. Through typical case analyses and multi-model comparisons, the characteristics of different models were analyzed in-depth, and the core value of organoid models in high-throughput drug screening, precision medicine practice, and personalized therapy exploration was explicitly highlighted. Studies have confirmed that organoid models can effectively compensate for the shortcomings of traditional models, holding promise as key tools to drive breakthroughs in PKD therapeutic research and opening new pathways for clinical translation. Meanwhile, this article scientifically prospects the future development directions of organoid models in the field of PKD research, aiming to provide references and inspiration for follow-up studies.

关键词

多囊肾 / 药物筛选 / 动物模型 / 类器官模型

Key words

polycystic kidney disease / drug screening / animal model / organoid model

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基金资助

深圳市科技重大专项资助项目(KJZD20240903102205008)