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Nephron organoids derived from human pluripotent stem cells model kidney development and injury

Nature Biotechnology volume 33, pages 11931200 (2015) | Download Citation


Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) may enable organ regeneration, disease modeling and drug screening. We report an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-organize into nephron structures. In both two- and three-dimensional culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.

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The authors thank V. Bijol for providing electron microscopy images of normal human kidneys, L. Racusen (Johns Hopkins Hospital) for HKC-8, J. Barasch (Columbia University) for a mouse ureteric bud cell line, and A.P. McMahon (University of Southern California) for NIH3T3-Wnt4. This study was supported by US National Institutes of Health (NIH) grants R37 DK039773 and R01 DK072381 (J.V.B.); Grant-in-Aid for JSPS (Japan Society for the Promotion of Science); Postdoctoral Fellowship for Research Abroad (R.M.); American Heart Association grant 11FTF7320023 (A.Q.L.); Harvard Stem Cell Institute (A.Q.L., J.V.B. and M.T.V.); and NIH DK102826 and National Kidney Foundation Young Investigator Grant (B.S.F.).

Author information


  1. Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Ryuji Morizane
    • , Albert Q Lam
    • , Benjamin S Freedman
    • , Seiji Kishi
    • , M Todd Valerius
    •  & Joseph V Bonventre
  2. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Ryuji Morizane
    • , Albert Q Lam
    • , Benjamin S Freedman
    • , Seiji Kishi
    • , M Todd Valerius
    •  & Joseph V Bonventre
  3. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.

    • Albert Q Lam
    • , M Todd Valerius
    •  & Joseph V Bonventre


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R.M. and J.V.B. formulated the strategy for this study. R.M. designed and performed experiments. R.M., A.Q.L. and J.V.B. wrote the manuscript. A.Q.L. and B.S.F. performed nephrotoxicity assays. S.K. performed real-time PCR. M.T.V. and J.V.B. helped to design experiments. All authors helped to interpret the results.

Competing interests

J.V.B. is a co-inventor on KIM-1 patents, which have been licensed by Partners Healthcare to several companies. He has received royalty income from Partners Healthcare. J.V.B. or his family has received income for consulting from companies interested in biomarkers: Sekisui, Millennium, Johnson & Johnson and Novartis.

Corresponding authors

Correspondence to Ryuji Morizane or Joseph V Bonventre.

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