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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月2日

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  • Murat Tekguc,
  • Takuya Matsumoto,
  • Lukas M. Altenburger,
  • Kenichi Kobayashi,
  • Ken Hiratsuka,
  • Yuhei Higashi,
  • Astia Rizki-Safitri,
  • Tomoya Miyoshi,
  • Wassim El-Jouni,
  • M. Amin Arnaout,
  • Thorsten R. Mempel,
  • Ryuji Morizane

摘要

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.