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Organoid research

Organoids are cell-derived in vitro 3D organ models and allow the study of biological processes, such as cell behaviour, tissue repair and response to drugs or mutations, in an environment that mimics endogenous cell organisation and organ structures. Starting as a major technological breakthrough they are now firmly established as an essential tool in biological research and also have important implications for clinical use. A major advantage is that organoids can be grown from a limited supply of starting material, e.g. biopsies, and used for drug screening to develop individual therapies. They have further shown potential in the modelling of diseases, gene editing and transplantations and not least helped to answer many important biological questions. Efforts are underway to setup cryopreserved biobanks of human organoids as a resource for researchers and clinicians.

Editorial and comment

Organoid technologies offer unique insights into the biological processes of the tissues they mimic and are being developed at a rapid pace. Here, we introduce a Collection of content from across the Nature Journals, outlining recent progress and challenges in the organoid field.

Editorial | | Nature Cell Biology

Current advances in biotechnology open up unprecedented possibilities to transform human tissues into complex, valuable tissue products, such as organoids. Here, we propose consent for governance as a leading paradigm for the derivation, storage and use of complex human tissue products to ensure adjustment to changing ethical requirements.

Comment | | Nature Cell Biology

Advances in stem cell research offer unprecedented insights into human biology and opportunities for clinical translation. They also raise many questions with social and ethical implications.

Editorial | | Nature Cell Biology

Three-dimensional brain organoid models have come into the spotlight as in vitro tools to recapitulate complex features of the brain. Four recent papers now leverage current technologies to generate new flavours of brain organoids and address aspects of brain biology which, to date, have been challenging to explore.

News & Views | | Nature Cell Biology

Organoids are a powerful tool to study both physiological and disease processes. A completely synthetic matrix assembled from exchangeable modular parts has been developed and not only supports proliferation of human intestinal organoids derived from pluripotent embryonic stem cells, but also augments subsequent ad vivo implantation into injured murine colon.

News & Views | | Nature Cell Biology

Difficult questions will be raised as models of the human brain get closer to replicating its functions, explain Nita A. Farahany, Henry T. Greely and 15 colleagues.

Comment | | Nature

Single-cell analyses in cancer are limited by the small biomass of individual cells. In vitro production of 3D organoid structures from single tumour-derived cells generates sufficient biomass for in-depth analyses.

News & Views | | Nature

In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.

News & Views | | Nature Medicine

Research articles

Human pluripotent stem cells were used to develop dorsal and ventral forebrain 3D spheroids, which can be assembled to study interneuron migration and to derive a functionally integrated forebrain system with cortical interneurons and glutamatergic neurons.

Article | | Nature

A protocol has been developed to use human induced pluripotent stem cells to obtain a self-formed ectodermal autonomous multizone, which includes distinct cell lineages of the eye, including the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium that can be expanded to form a functional corneal epithelium when transplanted to an animal model of corneal visual impairment.

Letter | | Nature

Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment.

Article | | Nature Medicine

A protocol based on chemical modulation of WNT activity is used to efficiently generate colonic organoids that recapitulate the molecular features of human colon tissue. Colonic organoids generated from induced pluripotent stem cells from patients with familial adenomatous polyposis provide an in vitro platform for disease modeling and preclinical drug testing.

Letter | | Nature Medicine

Organoids formed by combining pluripotent-stem-cell-derived human neural crest cells with pluripotent-stem-cell-derived intestinal tissue show functional interstitial cells of Cajal and undergo waves of contraction; these tissues reveal insights into the molecular defects characterizing Hirschsprung's disease.

Article | | Nature Medicine

Three-dimensional culture systems and organoids for mammary glands are important to understand mammary gland development. Here, the authors identify conditions (including Neuregulin 1 and R-spondin 1) that allow the culture of organoids that are responsive to hormonal stimulation for up to 2.5 months.

Article | open | | Nature Communications

Sensory hair cells from the mammalian inner ear do not regenerate. Here, the authors induce direct hair cell formation from mouse embryonic stem cells using a three-dimensional culture system and observe differentiation of Type I and Type II vestibular hair cells and establishment of synapses with neurons.

Article | open | | Nature Communications

There has been limited success in generating tissues from human induced pluripotent stem cells (hiPSCs). Here, the authors genetically engineer expression of the transcription factor Gata6 in a single isogenic hiPSC population resulting in complex tissue structures that exhibit liver bud-like properties.

Article | open | | Nature Communications

Reviews and Perspectives

In this Review, Drost and Clevers discuss the recent advances in organoid models of cancer and how they can be exploited to drive the translation of basic cancer research into novel patient-specific treatment regimens in the clinic.

Review Article | | Nature Reviews Cancer

3D organoids are valuable tools for increasing understanding of disease biology. In this Review, the authors describe how successful application of organoids into urological cancer research can further our understanding of these diseases and provide preclinical cancer models to aid precision medicine.

Review Article | | Nature Reviews Urology

Protocols