Scarlat Alexandru, Tomasoni Susanna, Trionfini Piera
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, Italy.
Biomedicines. 2025 Jul 18;13(7):1766. doi: 10.3390/biomedicines13071766.
Mutations in and cause autosomal dominant polycystic kidney disease (ADPKD), the most common renal genetic disease, leading to the dysregulation of renal tubules and the development of cystic growth that compromises kidney function. Despite significant advances in recent decades, there remains a considerable unmet clinical need, as current therapeutics are not effective at slowing or halting disease progression. Although preclinical animal models have been used extensively, the translatability of such findings is uncertain and human-relevant disease models are urgently needed. The advent of pluripotent stem cells (PSCs) and their ability to more accurately recapitulate organ architecture and function has allowed for the study of renal disease in a more physiological and human-relevant setting. To date, many research groups have studied ADPKD using PSC-derived kidney organoids, identifying many dysregulated pathways and screening drug candidates that may yield effective therapies in the clinic. In this review article, we discuss in detail the development of PSC-derived kidney organoids as ADPKD models and how they have advanced our understanding of the disease's pathogenesis, as well as their limitations and potential strategies to address them.
和中的突变会导致常染色体显性多囊肾病（ADPKD），这是最常见的肾脏遗传疾病，会导致肾小管失调以及囊肿生长，进而损害肾功能。尽管近几十年来取得了重大进展，但仍存在相当大的未满足临床需求，因为目前的治疗方法在减缓或阻止疾病进展方面并不有效。虽然临床前动物模型已被广泛使用，但这些研究结果的可转化性尚不确定，因此迫切需要与人类相关的疾病模型。多能干细胞（PSC）的出现及其更准确地再现器官结构和功能的能力，使得在更符合生理和人类实际情况的环境中研究肾脏疾病成为可能。迄今为止，许多研究小组利用PSC衍生的肾类器官对ADPKD进行了研究，确定了许多失调的通路，并筛选了可能在临床上产生有效治疗方法的候选药物。在这篇综述文章中，我们详细讨论了PSC衍生的肾类器官作为ADPKD模型的发展情况，以及它们如何增进了我们对该疾病发病机制的理解，同时也讨论了它们的局限性以及解决这些局限性的潜在策略。
