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Modeling Development and Disease with Organoids.
Literature Information
| DOI | 10.1016/j.cell.2016.05.082 |
|---|---|
| PMID | 27315476 |
| Journal | Cell |
| Impact Factor | 42.5 |
| JCR Quartile | Q1 |
| Publication Year | 2016 |
| Times Cited | 1468 |
| Keywords | Organoids, 3D culture technology, Regenerative medicine, Personalized drug response |
| Literature Type | Journal Article, Review |
| ISSN | 0092-8674 |
| Pages | 1586-1597 |
| Issue | 165(7) |
| Authors | Hans Clevers |
TL;DR
Recent advancements in 3D culture technology have enabled embryonic and adult stem cells to form organoids that mimic the structural and functional properties of various human organs, offering a valuable tool for modeling organ development and diseases. This technology, particularly through the use of patient-derived organoids, holds significant promise for personalized medicine, drug response prediction, and potential applications in regenerative medicine and gene therapy.
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Organoids · 3D culture technology · Regenerative medicine · Personalized drug response
Abstract
Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina. Organoid technology can therefore be used to model human organ development and various human pathologies 'in a dish." Additionally, patient-derived organoids hold promise to predict drug response in a personalized fashion. Organoids open up new avenues for regenerative medicine and, in combination with editing technology, for gene therapy. The many potential applications of this technology are only beginning to be explored.
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Primary Questions Addressed
- How can organoid technology be utilized to model specific diseases beyond the ones currently studied?
- What are the limitations of using organoids in drug response prediction compared to traditional methods?
- In what ways can gene editing technologies enhance the therapeutic potential of organoids in regenerative medicine?
- How do the structural and functional properties of organoids compare to those of the actual organs they represent?
- What ethical considerations arise from the use of patient-derived organoids in research and therapy?
Key Findings
1. Research Background and Purpose: The study of organ development and disease has traditionally relied on animal models and 2D cell cultures, which often fail to accurately replicate human organ systems. The recent advancements in 3D culture technology have enabled the cultivation of organoids—miniaturized, self-organizing structures derived from stem cells. These organoids mimic the structural and functional characteristics of various human organs, such as the kidney, lung, gut, brain, and retina. The purpose of this research is to explore the potential of organoids in modeling human organ development and disease, as well as their implications for personalized medicine and regenerative therapies.
2. Main Methods and Findings: The study utilizes advanced 3D culture techniques to cultivate both embryonic and adult mammalian stem cells, which exhibit self-organization to form organoids. These organoids are characterized by their ability to replicate key features of real organs, providing a more accurate platform for studying organ development and associated pathologies. Importantly, organoids derived from patient-specific cells have shown promise in predicting individual drug responses, thereby paving the way for personalized therapeutic approaches. The integration of gene editing technologies with organoid models further enhances their utility, allowing for targeted gene therapy and regenerative medicine applications.
3. Key Conclusions: Organoid technology represents a significant advancement in biomedical research, offering a viable in vitro model for studying human organ development and disease processes. The ability to create patient-derived organoids provides a powerful tool for personalized medicine, particularly in predicting drug efficacy and tailoring treatments to individual patients. The combination of organoid technology with gene editing holds exciting potential for developing novel therapies aimed at genetic disorders and regenerative medicine.
4. Research Significance and Impact: The implications of this research extend beyond basic biological understanding; they offer transformative potential in clinical applications. By providing a platform for modeling complex human diseases, organoids can facilitate drug discovery and testing, significantly reducing the reliance on animal models. Additionally, the personalized approach to treatment through patient-derived organoids may lead to improved patient outcomes and advancements in precision medicine. As the full potential of organoids is explored, they may revolutionize approaches to regenerative medicine, enabling the development of innovative therapies that could reshape the landscape of treatment for various diseases. Overall, this research highlights the critical role of 3D organoid culture in bridging the gap between laboratory research and clinical application.
Literatures Citing This Work
- Large variety in a panel of human colon cancer organoids in response to EZH2 inhibition. - Martijn A J Koppens;Gergana Bounova;Paulien Cornelissen-Steijger;Nienke de Vries;Owen J Sansom;Lodewyk F A Wessels;Maarten van Lohuizen - Oncotarget (2016)
- Organoid Culture of Human Cancer Stem Cells. - Yohei Shimono;Junko Mukohyama;Taichi Isobe;Darius M Johnston;Piero Dalerba;Akira Suzuki - Methods in molecular biology (Clifton, N.J.) (2019)
- Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration. - Sarah D Diermeier;Kung-Chi Chang;Susan M Freier;Junyan Song;Osama El Demerdash;Alexander Krasnitz;Frank Rigo;C Frank Bennett;David L Spector - Cell reports (2016)
- The development of anatomy: from macroscopic body dissections to stem cell-derived organoids. - Beate Brand-Saberi;Holm Zaehres - Histochemistry and cell biology (2016)
- Fluid Dynamic Modeling to Support the Development of Flow-Based Hepatocyte Culture Systems for Metabolism Studies. - Jenny M Pedersen;Yoo-Sik Shim;Vaibhav Hans;Martin B Phillips;Jeffrey M Macdonald;Glenn Walker;Melvin E Andersen;Harvey J Clewell;Miyoung Yoon - Frontiers in bioengineering and biotechnology (2016)
- Self-Organization of Stem Cell Colonies and of Early Mammalian Embryos: Recent Experiments Shed New Light on the Role of Autonomy vs. External Instructions in Basic Body Plan Development. - Hans-Werner Denker - Cells (2016)
- Nanomedicines for renal disease: current status and future applications. - Nazila Kamaly;John C He;Dennis A Ausiello;Omid C Farokhzad - Nature reviews. Nephrology (2016)
- Designer matrices for intestinal stem cell and organoid culture. - Nikolce Gjorevski;Norman Sachs;Andrea Manfrin;Sonja Giger;Maiia E Bragina;Paloma Ordóñez-Morán;Hans Clevers;Matthias P Lutolf - Nature (2016)
- Intestinal stem cell transplantation. - Tetsuya Nakamura;Mamoru Watanabe - Journal of gastroenterology (2017)
- A SILAC-Based Method for Quantitative Proteomic Analysis of Intestinal Organoids. - Alexis Gonneaud;Christine Jones;Naomie Turgeon;Dominique Lévesque;Claude Asselin;François Boudreau;François-Michel Boisvert - Scientific reports (2016)
... (1458 more literatures)
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