3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors

Zhongwei Li, Toshikazu Araoka, Jun Wu, Hsin Kai Liao, Mo Li, Marta Lazo, Bing Zhou, Yinghui Sui, Min Zu Wu, Isao Tamura, Yun Xia, Ergin Beyret, Taiji Matsusaka, Ira Pastan, Concepcion Rodriguez Esteban, Isabel Guillen, Pedro Guillen, Josep M. Campistol, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Transit-amplifying nephron progenitor cells (NPCs) generate all of the nephrons of the mammalian kidney during development. Their limited numbers, poor in vitro expansion, and difficult accessibility in humans have slowed basic and translational research into renal development and diseases. Here, we show that with appropriate 3D culture conditions, it is possible to support long-term expansion of primary mouse and human fetal NPCs as well as NPCs derived from human induced pluripotent stem cells (iPSCs). Expanded NPCs maintain genomic stability, molecular homogeneity, and nephrogenic potential in vitro, ex vivo, and in vivo. Cultured NPCs are amenable to gene targeting and can form nephron organoids that engraft in vivo, functionally couple to the host's circulatory system, and produce urine-like metabolites via filtration. Together, these findings provide a technological platform for studying human nephrogenesis, modeling and diagnosing renal diseases, and drug discovery.

Original languageEnglish (US)
Pages (from-to)516-529
Number of pages14
JournalCell Stem Cell
Volume19
Issue number4
DOIs
Publication statusPublished - Oct 6 2016
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Li, Z., Araoka, T., Wu, J., Liao, H. K., Li, M., Lazo, M., ... Izpisua Belmonte, J. C. (2016). 3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors. Cell Stem Cell, 19(4), 516-529. https://doi.org/10.1016/j.stem.2016.07.016