Rooney Kirsty M, Woolf Adrian S, Kimber Susan J
Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.
Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Nephron. 2021;145(3):285-296. doi: 10.1159/000514018. Epub 2021 Mar 26.
Kidney disease causes major suffering and premature mortality worldwide. With no cure for kidney failure currently available, and with limited options for treatment, there is an urgent need to develop effective pharmaceutical interventions to slow or prevent kidney disease progression.
In this review, we consider the feasibility of using human pluripotent stem cell-derived kidney tissues, or organoids, to model genetic kidney disease. Notable successes have been made in modelling genetic tubular diseases (e.g., cystinosis), polycystic kidney disease, and medullary cystic kidney disease. Organoid models have also been used to test novel therapies that ameliorate aberrant cell biology. Some progress has been made in modelling congenital glomerular disease, even though glomeruli within organoids are developmentally immature. Less progress has been made in modelling structural kidney malformations, perhaps because sufficiently mature metanephric mesenchyme-derived nephrons, ureteric bud-derived branching collecting ducts, and a prominent stromal cell population are not generated together within a single protocol. Key Messages: We predict that the field will advance significantly if organoids can be generated with a full complement of cell lineages and with kidney components displaying key physiological functions, such as glomerular filtration. The future economic upscaling of reproducible organoid generation will facilitate more widespread research applications, including the potential therapeutic application of these stem cell-based technologies.
肾脏疾病在全球范围内造成了巨大痛苦和过早死亡。目前尚无治愈肾衰竭的方法，治疗选择有限，因此迫切需要开发有效的药物干预措施来减缓或预防肾脏疾病的进展。
在本综述中，我们探讨了使用人多能干细胞衍生的肾脏组织或类器官来模拟遗传性肾脏疾病的可行性。在模拟遗传性肾小管疾病（如胱氨酸病）、多囊肾病和髓质囊性肾病方面已取得显著成功。类器官模型也已用于测试改善异常细胞生物学的新疗法。在模拟先天性肾小球疾病方面已取得一些进展，尽管类器官内的肾小球在发育上不成熟。在模拟肾脏结构畸形方面进展较小，这可能是因为在单一方案中无法同时生成足够成熟的后肾间充质衍生的肾单位、输尿管芽衍生的分支集合管和突出的基质细胞群。关键信息：我们预测，如果能够生成具有完整细胞谱系且肾脏成分显示关键生理功能（如肾小球滤过）的类器官，该领域将取得显著进展。可重复生成类器官的未来经济规模化将促进更广泛的研究应用，包括这些基于干细胞技术的潜在治疗应用。
