2. Academic Validation
  3. Developmental Hypoxia Enhances Kidney Organoid Complexity and Maturity

Developmental Hypoxia Enhances Kidney Organoid Complexity and Maturity

  • Adv Sci (Weinh). 2025 Aug 21:e01661. doi: 10.1002/advs.202501661.
Hyeonji Lim 1,  Dohui Kim 2,  Haejin Yoon 3,  Joo H Kang 1,  Yong Jun Kim 4,  Dong Sung Kim 2 5 6 7,  Tae-Eun Park 1
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
  • 2 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
  • 3 Department of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
  • 4 Department of Pathology, College of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
  • 5 Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
  • 6 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
  • 7 Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, 03722, Republic of Korea.
PMID: 40841925 DOI: 10.1002/advs.202501661
Abstract

Reciprocal signaling between metanephric mesenchyme (MM) and ureteric bud (UB) is essential for human kidney development. However, human pluripotent stem cell-derived kidney organoids do not incorporate UB differentiation, limiting Organoid maturation and disease modeling. Here, a hypoxia-based differentiation method inspired by developmental cues is reported that produces mature kidney organoids with collecting duct-like tubules connected to multiple nephrons. Hypoxia promotes the co-induction of MM and UB-like progenitors within the same culture dish. The augmented expression of reciprocal signaling genes guides the differentiation of the kidney organoids into highly structured tubular networks, mature RNA profiles, and a more realistic micro-anatomy, leading to higher-order kidney organogenesis in vitro. These hypoxia-enhanced kidney organoids recapitulate the cystic phenotype in polycystic kidney disease, displaying efficient cyst formation across the entire tubular region and increased sensitivity to drugs. The findings provide an improved in vitro model for studying kidney development and disease mechanisms.

Keywords

human induced pluripotent stem cell; hypoxia; kidney organoid; nephrogenesis; polycystic kidney disease.

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