Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling.
Publication Year:
2025
PubMed ID:
40967224
Funding Grants:
Public Summary:
Scientists are trying to grow miniature kidneys in the lab, but current models don’t fully mimic the real organ’s complex structure or function. In this study, researchers created new “kidney progenitor assembloids” (KPAs) using mouse and human cells. These KPAs can organize themselves into structures that closely resemble real kidneys, with developing nephrons connecting to a central collecting system—just as they do in the body. The resulting tissues are more mature, more complex, and able to perform several key kidney functions both in lab dishes and after being transplanted into animals. When used to model polycystic kidney disease, the KPAs developed cysts and other hallmark features of the disorder, offering valuable insight into how different kidney cell types interact during disease. This new platform could greatly improve disease research and advance future kidney regeneration therapies.
Scientific Abstract:
Current kidney organoids do not recapitulate the kidney's complex spatial patterning and function, limiting their applications. The human kidney comprises one million nephrons, derived from nephron progenitor cells, that connect to an arborized ureteric progenitor cell-derived collecting system. Here, we develop spatially organized mouse and human kidney progenitor assembloid (KPA) models in which the nephrons undergo extensive development and fuse to a centrally located collecting system, recapitulating kidney progenitor self-assembly processes observed in vivo. KPAs show dramatically improved cellular complexity and maturity and exhibit several aspects of major kidney functions in vitro and in vivo. Modeling human autosomal dominant polycystic kidney disease (ADPKD) with genome-edited, in vivo-grown human KPAs recapitulated the cystic phenotype and the molecular and cellular hallmarks of the disease and highlighted the crosstalk among cyst epithelium, stroma, and macrophages. The KPA platform opens new avenues for high-fidelity disease modeling and lays a strong foundation for kidney regenerative medicine.
