Engineering scalable vascularized kidney organoids for in vivo glomerular filtration with human endothelial integration

Kidney organoids derived from human pluripotent stem cells have emerged as promising models for studying kidney disease and therapeutic development. However, the lack of a scalable production system has limited their industrial applications in regenerative medicine. Here, we have developed a cost-effective mass-production method for manufacturing vascularized kidney organoids, which has improved production efficiency by more than 50 times compared to conventional culture systems. The incorporation of a dynamic culture environment in delta-wing stirred bioreactors has significantly enhanced the glomerular vascularization of kidney organoids via mechanosensory integrin α2β1. Single-cell RNA sequencing and functional analyses demonstrated the enhanced maturation in STR nephron epithelia. The large quantities of vascularized kidney organoids enabled the fabrication of a nephron sheet with nephron numbers equivalent to those found in two rat kidneys. Intravital imaging of a nephron sheet implanted in a dorsal skinfold chamber of mice revealed filtration function with size selectability in the organoid glomeruli vascularized with human endothelia. This work may represent a significant step towards bridging the gap between basic research and commercial products, paving the way towards developing bioengineered kidneys for kidney replacement therapy.