Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

Organoids in endocrine and metabolic research: current and emerging applications

Nature Reviews Endocrinology volume 20, pages 195–201 (2024)Cite this article

Subjects

Organoid technologies are a potent tool for investigating human biology, modelling diseases and developing novel therapies. In this Viewpoint, experts in metabolic and endocrine research in the brain, pituitary, skeletal muscle, bone and gastrointestinal system discuss how organoids and related bioengineered systems are currently used in their field and how innovations in these technologies could transform future research.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Rajamani, U. et al. Super-obese patient-derived iPSC hypothalamic neurons exhibit obesogenic signatures and hormone responses. Cell Stem Cell 22, 698–712 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Matsumoto, R. et al. Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells. J. Clin. Invest. 130, 641–654 (2020).

    Article  PubMed  Google Scholar 

  3. Laporte, E. et al. Decoding the activated stem cell phenotype of the neonatally maturing pituitary. eLife 11, e75742 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vennekens, A. et al. Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland. Proc. Natl Acad. Sci. USA 118, e2100052118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bakooshli, M. A. et al. A 3d culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction. eLife 8, e44530 (2019).

    Article  CAS  Google Scholar 

  6. Faustino Martins, J. M. et al. Self-organizing 3D human trunk neuromuscular organoids. Cell Stem Cell 26, 172–186 (2020).

    Article  CAS  PubMed  Google Scholar 

  7. Sylow, L., Tokarz, V. L., Richter, E. A. & Klip, A. The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia. Cell Metab. 33, 758–780 (2021).

    Article  CAS  PubMed  Google Scholar 

  8. Buss, D. J. et al. Hierarchical organization of bone in three dimensions: a twist of twists. J. Struct. Biol. X 6, 100057 (2022).

    MathSciNet  CAS  PubMed  Google Scholar 

  9. Akiva, A. et al. An organoid for woven bone. Adv. Funct. Mater. 31, 2010524 (2021).

    Article  CAS  Google Scholar 

  10. de Wildt, B. W. M. et al. Bioinspired silk fibroin mineralization for advanced in vitro bone remodeling models. Adv. Funct. Mater. 32, 2206992 (2022).

    Article  Google Scholar 

  11. Krishnamurthy, M. et al. Using human induced pluripotent stem cell-derived organoids to identify new pathologies in patients with PDX1 mutations. Gastroenterology 163, 1053–1063 (2022).

    Article  CAS  PubMed  Google Scholar 

  12. Huang, W.-K. et al. Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells. Cell Stem Cell 28, 1657–1670 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Miwata, T. et al. Generation of hypothalamic neural stem cell-like cells in vitro from human pluripotent stem cells. Stem Cell Rep. 18, 869–883 (2023).

    Article  CAS  Google Scholar 

  14. Nys, C. et al. Exploring stem cell biology in pituitary tumors and derived organoids. Endocr. Relat. Cancer 29, 427–450 (2022).

    Article  CAS  PubMed  Google Scholar 

  15. Chakrabarti, J. et al. Development of human pituitary neuroendocrine tumor organoids to facilitate effective targeted treatments of Cushings disease. Cells 11, 3344 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fernández-Costa, J. M. et al. Training-on-a-chip: a multi-organ device to study the effect of muscle exercise on insulin secretion in vitro. Adv. Mater. Technol. 8, 2200873 (2023).

    Article  Google Scholar 

  17. Vis, M. A. M., de Wildt, B. W. M., Ito, K. & Hofmann, S. A dialysis medium refreshment cell culture set-up for an osteoblast-osteoclast coculture. Biotech. Bioeng. 120, 1120–1132 (2023).

    Article  CAS  Google Scholar 

  18. Eicher, A. K. et al. Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells. Cell Stem Cell 29, 36–51 (2022).

    Article  CAS  PubMed  Google Scholar 

  19. Workman, M. et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat. Med. 23, 49–59 (2017).

    Article  CAS  PubMed  Google Scholar 

  20. Múnera, J. O. et al. Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. Cell Stem Cell 30, 1434–1451 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kasai, T. et al. Hypothalamic contribution to pituitary functions is recapitulated in vitro using 3D-cultured human iPS cells. Cell Rep. 30, 18–24 (2020).

    Article  CAS  PubMed  Google Scholar 

  22. Molendijk, J. et al. Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function. eLife 11, e82951 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McCauley, H. A., Matthis, A. L. & Enriquez, J. R. et al. Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport. Nat. Commun. 11, 4791 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Melton, D. The promise of stem cell-derived islet replacement therapy. Diabetologia 64, 1030–1036 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

P.M.G. is cross-appointed to the Donnelly Centre and to the Department of Cell and Systems Biology at the University of Toronto. H.H.N. is supported by grants from the Agency for Science, Technology and Research (A*STAR) and the National Medical Research Council of Singapore. H.H.N. is grateful to Dr Alfred Sun (Duke-NUS Medical School) for discussion during the preparation of this manuscript. H.V. was supported by grants from the KU Leuven Research Fund and the Fund for Scientific Research (FWO) – Flanders (Belgium).

Author information

Authors and Affiliations

  1. Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

    Penney M. Gilbert

  2. Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

    Sandra Hofmann

  3. Laboratory of Precision Disease Therapeutics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Huck-Hui Ng

  4. Department of Development and Regeneration, Cluster of Stem Cell and Developmental Biology, KU Leuven, Leuven, Belgium

    Hugo Vankelecom

  5. Division of Developmental Biology, Division of Endocrinology, Center for Stem Cell and Organoid Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    James M. Wells

Authors
  1. Penney M. Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huck-Hui Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hugo Vankelecom
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James M. Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Penney M. Gilbert, Sandra Hofmann, Huck-Hui Ng, Hugo Vankelecom or James M. Wells.

Ethics declarations

Competing interests

J.M.W. holds patents for intestinal and gastric organoids licensed by STEMCELL technologies. The other authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The Contributors

Penney M. Gilbert is an Associate Professor at the University of Toronto in the Institute of Biomedical Engineering where she holds the Canada Research Chair in Endogenous Repair. She is co-director of the PREDICT consortium.

Sandra Hofmann is an Associate Professor at the Eindhoven University of Technology. Her research focuses on bioengineering skeletal tissues, with an emphasis on bone. Her work is characterized by a keen interest in understanding how cells react to environmental parameters in tissue-engineered in vitro models of bone tissue, including bone organoids.

Huck-Hui Ng is a Senior Group Leader at the Genome Institute of Singapore at the Agency for Science, Technology and Research (A*STAR) and an Adjunct Professor at the National University of Singapore and the Nanyang Technological University. He has made significant contributions to the fields of stem cell biology, gene regulatory networks, genomics and organoids, and has multiple appointments with A*STAR and other organizations.

Hugo Vankelecom obtained his PhD at KU Leuven and is a professor at the Stem Cell and Developmental Biology unit at that university. He leads a group specializing in pituitary (and reproductive) research, which discovered pituitary stem cells and developed an innovative pituitary stem cell organoid model. His research focuses on pituitary stem cell biology and tumorigenesis in the gland.

James M. Wells is an endowed professor in the Division of Developmental Biology at Cincinnati Children’s Hospital Research Foundation and is the Director of Basic Research in the Division of Endocrinology. He is a co-founder and Chief Scientific Officer of the Center for Stem Cell and Organoid Medicine.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gilbert, P.M., Hofmann, S., Ng, HH. et al. Organoids in endocrine and metabolic research: current and emerging applications. Nat Rev Endocrinol 20, 195–201 (2024). https://doi.org/10.1038/s41574-023-00933-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-023-00933-1

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing