Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences, Utrecht, the Netherlands.
Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, the Netherlands.
Nat Biotechnol. 2019 Mar;37(3):303-313. doi: 10.1038/s41587-019-0048-8. Epub 2019 Mar 4.
Adult stem cell-derived organoids are three-dimensional epithelial structures that recapitulate fundamental aspects of their organ of origin. We describe conditions for the long-term growth of primary kidney tubular epithelial organoids, or 'tubuloids'. The cultures are established from human and mouse kidney tissue and can be expanded for at least 20 passages (>6 months) while retaining a normal number of chromosomes. In addition, cultures can be established from human urine. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. We apply tubuloids to model infectious, malignant and hereditary kidney diseases in a personalized fashion. BK virus infection of tubuloids recapitulates in vivo phenomena. Tubuloids are established from Wilms tumors. Kidney tubuloids derived from the urine of a subject with cystic fibrosis allow ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function.
成人干细胞来源的类器官是三维上皮结构，可再现其起源器官的基本方面。我们描述了长期培养原代肾小管上皮类器官（“小管类器官”）的条件。这些培养物来源于人和小鼠的肾脏组织，可至少扩增 20 代（>6 个月），同时保持正常数量的染色体。此外，还可以从小便中建立人类类器官培养物。人类小管类器官代表近端和远端肾单位，这可以通过基因表达、免疫荧光和管状功能分析来证明。我们以个性化的方式将小管类器官应用于感染性、恶性和遗传性肾脏疾病的模型中。BK 病毒感染小管类器官再现了体内现象。从小儿肾母细胞瘤中建立了小管类器官。从小患有囊性纤维化的患者尿液中分离出的肾小管类器官可以在体外评估治疗效果。最后，在微流控器官芯片板上培养的小管类器官采用管状构象，并显示出活跃的（跨）上皮转运功能。
