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Engineering kidney cells: reprogramming and directed differentiation to renal tissues

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Abstract

Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

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Acknowledgements

This work was supported by the Emmy Noether Programme to S.S.L. (LI1817/2-1) and S.J.A. (AR732/1-1), by Project B07 of the Collaborative Research Initiative (SFB 1140 - KIDGEM) of the German Research Foundation (DFG) to S.S.L. and S.J.A., by the BIOSS Centre of Biological Signalling Studies and the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School) to S.J.A.

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Authors and Affiliations

  1. Department of Medicine, Renal Division, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Michael M. Kaminski, Roman Pichler & Soeren S. Lienkamp

  2. Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany

    Jelena Tosic & Sebastian J. Arnold

  3. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstrasse 19a, 79104, Freiburg, Germany

    Jelena Tosic

  4. Faculty of Biology, University of Freiburg, Schänzlestrasse 1, 79104, Freiburg, Germany

    Jelena Tosic

  5. BIOSS Centre of Biological Signalling Studies, University of Freiburg, Schänzlestrasse 18, 79104, Freiburg, Germany

    Sebastian J. Arnold & Soeren S. Lienkamp

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  1. Michael M. Kaminski
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  2. Jelena Tosic
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  3. Roman Pichler
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  4. Sebastian J. Arnold
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  5. Soeren S. Lienkamp
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Correspondence to Soeren S. Lienkamp.

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Kaminski, M.M., Tosic, J., Pichler, R. et al. Engineering kidney cells: reprogramming and directed differentiation to renal tissues. Cell Tissue Res 369, 185–197 (2017). https://doi.org/10.1007/s00441-017-2629-5

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  • DOI: https://doi.org/10.1007/s00441-017-2629-5

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