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Towards a better understanding of diabetes mellitus using organoid models

Nature Reviews Endocrinology volume 19, pages 232–248 (2023)Cite this article

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Abstract

Our understanding of diabetes mellitus has benefited from a combination of clinical investigations and work in model organisms and cell lines. Organoid models for a wide range of tissues are emerging as an additional tool enabling the study of diabetes mellitus. The applications for organoid models include studying human pancreatic cell development, pancreatic physiology, the response of target organs to pancreatic hormones and how glucose toxicity can affect tissues such as the blood vessels, retina, kidney and nerves. Organoids can be derived from human tissue cells or pluripotent stem cells and enable the production of human cell assemblies mimicking human organs. Many organ mimics relevant to diabetes mellitus are already available, but only a few relevant studies have been performed. We discuss the models that have been developed for the pancreas, liver, kidney, nerves and vasculature, how they complement other models, and their limitations. In addition, as diabetes mellitus is a multi-organ disease, we highlight how a merger between the organoid and bioengineering fields will provide integrative models.

Key points

  • Pancreas and islet organoids enable the study of monogenic forms of diabetes mellitus, notably neonatal diabetes mellitus.

  • For type 1 diabetes mellitus, platforms mixing patient-relevant islets and immune cells are expanding.

  • Organoid models are emerging that combine cell types derived from multiple organs relevant to diabetes mellitus.

  • A merger between bioengineering techniques and organoid technology is improving functional and screening assays.

  • For assays of organ interactions, organ-on-a-chip platforms are moving from cell lines to organoids.

  • While organoid models for diabetes mellitus complications are being added to the toolbox, the long periods over which complications develop mean that studying these complications in vitro will be challenging.

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Fig. 1: Types of 3D cultures modelling pancreas and islet development, physiology and disease.
Fig. 2: Novel and emerging organoid culture systems using microfluidics.
Fig. 3: Organoid systems of different complexity, enabling interactions between cells and organs in the course of diabetes mellitus to be studied.
Fig. 4: Diabetes mellitus complication problems that might be solved with organoids.

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Authors and Affiliations

  1. The Novo Nordisk Foundation Center for Stem Cell Biology, Copenhagen, Denmark

    Belin Selcen Beydag-Tasöz & Siham Yennek

  2. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

    Belin Selcen Beydag-Tasöz & Anne Grapin-Botton

  3. Paul Langerhans Institute Dresden, Dresden, Germany

    Anne Grapin-Botton

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A.G.-B. and B.S.B.-T. researched data for the article, contributed substantially to discussion of content, wrote the article and reviewed/edited the article before submission. S.Y. researched data for the article, contributed substantially to discussion of content and wrote the article.

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Beydag-Tasöz, B.S., Yennek, S. & Grapin-Botton, A. Towards a better understanding of diabetes mellitus using organoid models. Nat Rev Endocrinol 19, 232–248 (2023). https://doi.org/10.1038/s41574-022-00797-x

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