Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder affecting 1:400-1,000 people in the world. 85% of ADPKD is caused by mutations in PKD1, and PKD2 mutations are responsable for the rest. ADPKD is characterized by multiple cyst formations in the kidney which impair the organ function and may lead to kidney failure. Currently no treatment is available for ADPKD. Although many disease models have been proposed for ADPKD, genetically relevant human models suitable for high throughput drug screening are still lacking.
Technical Summary
The researchers developed an ADPKD model based on kidney organoids derived from induced pluripotent stem cells (iPSCs). iPSCs were derived from ADPKD patients and induced to differentiate into kidney cells forming organoids with cystic structures.
➤ Uretetic bud organoids are generated
In addition to cyst-forming nephron organoids (Shimizu et al. 2020), the researchers established a method of generating ureteric bud (UB) organoids and managed to induce cystogenesis in them too (Kuraoka et al. 2020, Fig. 1). This is important
because large cysts in patients with ADPKD tend to originate from collecting ducts rather than nephron tubules.
➤ High throughput drug screening can be performed
Conventional nephron organoids lack the UB/collecting duct lineage therefore failing to recaputulate the disease. Because the organoids are obtained from patient-derived iPSCs, our model is applicable to various PKD1 alleles observed in
patients. Moreover, the researchers confirmed that these organoids can be used as screening platforms for ADPKD therapeutic candidates. Therefore, the system can be used as an accurate ADPKD model for, but not limited to, high throughput drug screening.
Current development status
ADPKD model has been validated to have predictive value for drug screening
Applications
Intellectual Property
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