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Organogenesis in a dish: modeling development and disease using organoid technologies.
Literature Information
| PMID | 25035496 |
|---|---|
| Journal | Science (New York, N.Y.) |
| Impact Factor | 45.8 |
| JCR Quartile | Q1 |
| Publication Year | 2014 |
| Times Cited | 1360 |
| Keywords | Organ development, Organoid technology, Stem cells, Disease modeling, Drug testing |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 0036-8075 |
| Pages | 1247125 |
| Issue | 345(6194) |
| Authors | Madeline A Lancaster, Juergen A Knoblich |
TL;DR
This paper reviews the advancements in organoid technology, which leverages the self-organizing ability of vertebrate cells to create three-dimensional cultures from human and patient-derived stem cells. The findings highlight organoids' potential for modeling human development and diseases, as well as their applications in drug testing and organ replacement strategies, underscoring their significance in future biomedical research.
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Organ development · Organoid technology · Stem cells · Disease modeling · Drug testing
Abstract
Classical experiments performed half a century ago demonstrated the immense self-organizing capacity of vertebrate cells. Even after complete dissociation, cells can reaggregate and reconstruct the original architecture of an organ. More recently, this outstanding feature was used to rebuild organ parts or even complete organs from tissue or embryonic stem cells. Such stem cell-derived three-dimensional cultures are called organoids. Because organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they have the potential to model human development and disease. Furthermore, they have potential for drug testing and even future organ replacement strategies. Here, we summarize this rapidly evolving field and outline the potential of organoid technology for future biomedical research.
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Primary Questions Addressed
- How do organoids mimic the complexity of actual organs in terms of cellular interactions and functions?
- What are the current limitations of using organoids for modeling specific diseases, and how might these be overcome?
- In what ways can organoid technologies contribute to personalized medicine and tailored treatment strategies?
- How does the use of patient-derived induced pluripotent stem cells enhance the relevance of organoid models in disease research?
- What ethical considerations arise from the use of organoid technologies in biomedical research and potential therapeutic applications?
Key Findings
Key Insights
Research Background and Purpose: The study of organogenesis has evolved significantly over the past fifty years, revealing the remarkable self-organizing properties of vertebrate cells. Classical experiments demonstrated that even when cells are dissociated, they have the ability to reaggregate and reconstruct the architecture of organs. The purpose of this research is to explore and summarize the advancements in organoid technologies, which utilize these self-organizing capacities to model human organ development and disease. This emerging field aims to bridge the gap between basic biological research and practical applications in medicine, including drug testing and regenerative therapies.
Main Methods and Findings: The research highlights the development of organoids, which are three-dimensional cultures derived from human stem cells or patient-specific induced pluripotent stem cells (iPSCs). These organoids mimic the structure and function of real organs, allowing researchers to study various aspects of human biology in vitro. Key findings indicate that organoids can replicate not only the architecture of organs but also their physiological functions, making them powerful tools for modeling diseases. Additionally, organoids can be used for drug testing, providing a more relevant biological context compared to traditional two-dimensional cell cultures. The ability to derive organoids from individual patients offers a personalized approach to studying disease mechanisms and treatment responses.
Core Conclusions: The study concludes that organoid technology represents a significant advancement in the field of biomedical research. By utilizing stem cell-derived organoids, researchers can effectively model human organ development and disease mechanisms. The ability to create organoids from patient-specific cells holds promise for personalized medicine, enabling tailored therapeutic strategies. Furthermore, organoids provide a platform for high-throughput drug screening, potentially accelerating the discovery of effective treatments.
Research Significance and Impact: The implications of this research are profound, as organoid technology has the potential to revolutionize how we understand human biology and disease. By creating accurate models of human organs, scientists can investigate complex biological processes and disease pathways in ways that were previously unattainable. Additionally, the application of organoids in drug testing can lead to more effective and safer therapeutic options, significantly impacting clinical outcomes. As organoid technology continues to evolve, it could pave the way for innovative organ replacement strategies, addressing organ donor shortages and improving regenerative medicine practices. Overall, this research underscores the transformative power of organoids in shaping the future of biomedical research and healthcare.
Literatures Citing This Work
- Single luminal epithelial progenitors can generate prostate organoids in culture. - Chee Wai Chua;Maho Shibata;Ming Lei;Roxanne Toivanen;LaMont J Barlow;Sarah K Bergren;Ketan K Badani;James M McKiernan;Mitchell C Benson;Hanina Hibshoosh;Michael M Shen - Nature cell biology (2014)
- Human pluripotent stem cell-derived products: advances towards robust, scalable and cost-effective manufacturing strategies. - Michael J Jenkins;Suzanne S Farid - Biotechnology journal (2015)
- Genetic regulation of murine pituitary development. - Karine Rizzoti - Journal of molecular endocrinology (2015)
- Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology. - Alicia K Olivier;Katherine N Gibson-Corley;David K Meyerholz - American journal of physiology. Gastrointestinal and liver physiology (2015)
- Muscling in on the third dimension. - Mohsen Afshar Bakooshli;Penney M Gilbert - eLife (2015)
- Primary retinal cultures as a tool for modeling diabetic retinopathy: an overview. - Andrea Matteucci;Monica Varano;Cinzia Mallozzi;Lucia Gaddini;Marika Villa;Sara Gabrielli;Giuseppe Formisano;Flavia Pricci;Fiorella Malchiodi-Albedi - BioMed research international (2015)
- Micropatterned, clickable culture substrates enable in situ spatiotemporal control of human PSC-derived neural tissue morphology. - G T Knight;J Sha;R S Ashton - Chemical communications (Cambridge, England) (2015)
- In vivo reprogramming for tissue repair. - Christophe Heinrich;Francesca M Spagnoli;Benedikt Berninger - Nature cell biology (2015)
- Advances in reprogramming-based study of neurologic disorders. - Anjana Nityanandam;Kristin K Baldwin - Stem cells and development (2015)
- Reprogramming for cardiac regeneration. - Christophe Michel Raynaud;Faizzan Syed Ahmad;Mona Allouba;Haissam Abou-Saleh;Kathy O Lui;Magdi Yacoub - Global cardiology science & practice (2014)
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