Letter | Published:

Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells

Nature Cell Biology volume 15, pages 15071515 (2013) | Download Citation

Abstract

Diseases affecting the kidney constitute a major health issue worldwide. Their incidence and poor prognosis affirm the urgent need for the development of new therapeutic strategies. Recently, differentiation of pluripotent cells to somatic lineages has emerged as a promising approach for disease modelling and cell transplantation. Unfortunately, differentiation of pluripotent cells into renal lineages has demonstrated limited success. Here we report on the differentiation of human pluripotent cells into ureteric-bud-committed renal progenitor-like cells. The generated cells demonstrated rapid and specific expression of renal progenitor markers on 4-day exposure to defined media conditions. Further maturation into ureteric bud structures was accomplished on establishment of a three-dimensional culture system in which differentiated human cells assembled and integrated alongside murine cells for the formation of chimeric ureteric buds. Altogether, our results provide a new platform for the study of kidney diseases and lineage commitment, and open new avenues for the future application of regenerative strategies in the clinic.

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Acknowledgements

We thank M. Schwarz for administrative support. We thank J. Kasuboski from Waitt Advanced Biophotonics Core at Salk for help with imaging processing. We thank B. C. Lu for his suggestions regarding kidney dissection and organ culture. Y.X. and K.S. were partially supported by the California Institute for Regenerative Medicine. I.S-M. was partially supported by a Nomis Foundation postdoctoral fellowship. Work in the laboratory of J.C.I.B. was supported by grants from Fundacion Cellex, the G. Harold and L. Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, IPSEN Foundation, Fundació La Marató de TV3 (121330), CIBER BBN and ISCIII-TERCEL-MINECO.

Author information

Author notes

    • Yun Xia
    • , Emmanuel Nivet
    •  & Ignacio Sancho-Martinez

    These authors contributed equally to this work

Affiliations

  1. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA

    • Yun Xia
    • , Emmanuel Nivet
    • , Ignacio Sancho-Martinez
    • , Thomas Gallegos
    • , Keiichiro Suzuki
    • , Daiji Okamura
    • , Min-Zu Wu
    • , Ilir Dubova
    • , Concepcion Rodriguez Esteban
    •  & Juan Carlos Izpisua Belmonte
  2. Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona, Spain

    • Ignacio Sancho-Martinez
    • , Nuria Montserrat
    •  & Juan Carlos Izpisua Belmonte
  3. Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 50018 Barcelona, Spain

    • Nuria Montserrat
  4. Renal Division, Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain

    • Josep M. Campistol

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Contributions

Y.X., I.S-M., E.N. and J.C.I.B. designed all experiments. Y.X., I.S-M., E.N. and J.C.I.B. wrote the manuscript. Y.X., I.S-M., T.G. and E.N. performed and analysed all experiments. D.O., I.D., C.R.E. and Y.X. performed in vivo experiments. N.M. was responsible for cell culture and maintenance of the patient samples related to this work. K.S. and M-Z.W. provided reagents. J.M.C. contributed to the overall design of the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Juan Carlos Izpisua Belmonte.

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DOI

https://doi.org/10.1038/ncb2872