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Replacing renal function using bioengineered tissues

Nature Reviews Bioengineering volume 1, pages 576–588 (2023)Cite this article

Subjects

Abstract

Kidney transplantation is at present the only definitive treatment for patients with end-stage kidney disease that can improve the quality of life compared with dialysis. However, donor organs are of limited availability. The question is whether kidney tissues can be engineered to provide renal replacement therapy. In this Review, we outline key challenges in renal replacement and examine the clinical potential, current limitations and ethical considerations of bioengineering approaches aimed at replacing renal function, including kidney decellularization and recellularization, ex vivo kidney engineering, xenotransplantation, blastocyst complementation and kidneys derived from pluripotent stem cells. Finally, we highlight key hurdles that remain to be addressed to translate bioengineered kidney approaches to the clinic, including product scalability, ex vivo tissue preservation and good manufacturing practice.

Key points

  • Treatment options for end-stage kidney disease rely on dialysis and organ transplantation, with limited organ availability.

  • Kidney tissue can be bioengineered for renal replacement therapy, including engineering non-human hosts for xenotransplantation or blastocyst complementation, rebuilding functional kidney tissue from stem cells, kidney decellularization and recellularization, and ex vivo kidney engineering.

  • Each approach presents different ethical, technical, immunological and manufacturing challenges.

  • Translation of engineered kidney replacement strategies will require scale-up, ex vivo tissue preservation strategies and a regulatory framework.

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Fig. 1: Xenotransplantation from hypoimmunogenic pigs.
Fig. 2: Engineering the host pig and human donor for blastocyst complementation to create human organs for transplantation.
Fig. 3: Human pluripotent-stem-cell-derived kidney tissue for renal replacement.
Fig. 4: Engineering kidney from pluripotent stem cells.

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Acknowledgements

M.H.L. and T.J.R. are funded by the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) supported by a grant from the Novo Nordisk Foundation (NNF21CC0073729).

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Authors and Affiliations

  1. Novo Nordisk Foundation Center for Stem Cell Medicine, University of Copenhagen, Copenhagen, Denmark

    Melissa H. Little

  2. Murdoch Children’s Research Institute, Parkville, Victoria, Australia

    Melissa H. Little

  3. Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia

    Melissa H. Little

  4. Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

    Ton J. Rabelink

  5. Novo Nordisk Foundation Center for Stem Cell Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Ton J. Rabelink

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Both authors contributed equally to the content of this Review.

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Correspondence to Melissa H. Little.

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Competing interests

M.H.L. is an inventor on intellectual property in the field of stem-cell-derived kidney tissue. M.H.L. and T.J.R. have received unrestricted research funding from Novo Nordisk A/S.

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Nature Reviews Bioengineering thanks Harald Ott, Ryuichi Nishinakamura and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Guidelines from the International Society for Stem Cell Research: https://www.isscr.org/guidelines

In 2021, 97,376 patients awaited kidney transplantation in the United States: https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#

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Little, M.H., Rabelink, T.J. Replacing renal function using bioengineered tissues. Nat Rev Bioeng 1, 576–588 (2023). https://doi.org/10.1038/s44222-023-00066-0

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