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A brief history of organoids.
Literature Information
| DOI | 10.1152/ajpcell.00120.2020 |
|---|---|
| PMID | 32459504 |
| Journal | American journal of physiology. Cell physiology |
| Impact Factor | 4.7 |
| JCR Quartile | Q1 |
| Publication Year | 2020 |
| Times Cited | 229 |
| Keywords | disease modeling, organoids, precision medicine, regenerative medicine |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 0363-6143 |
| Pages | C151-C165 |
| Issue | 319(1) |
| Authors | Claudia Corrò, Laura Novellasdemunt, Vivian S W Li |
TL;DR
This review discusses the evolution of organoid technology, which provides advanced three-dimensional in vitro models that mimic the complexity and functionality of human tissues, overcoming the limitations of traditional monolayer cultures. The findings highlight the significant potential of organoids in regenerative medicine, drug discovery, and precision medicine, emphasizing their importance for both laboratory research and clinical applications.
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disease modeling · organoids · precision medicine · regenerative medicine
Abstract
In vitro cell cultures are crucial research tools for modeling human development and diseases. Although the conventional monolayer cell cultures have been widely used in the past, the lack of tissue architecture and complexity of such model fails to inform the true biological processes in vivo. Recent advances in the organoid technology have revolutionized the in vitro culture tools for biomedical research by creating powerful three-dimensional (3D) models to recapitulate the cellular heterogeneity, structure, and functions of the primary tissues. Such organoid technology enables researchers to recreate human organs and diseases in a dish and thus holds great promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. In this review, we provide an overview of the organoid history and development. We discuss the strengths and limitations of organoids as well as their potential applications in the laboratory and the clinic.
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Primary Questions Addressed
- What specific advancements in organoid technology have significantly impacted drug discovery processes?
- How do organoids compare to other in vitro models in terms of mimicking human tissue architecture?
- What are the key challenges researchers face when developing organoids for regenerative medicine applications?
- In what ways can organoids be utilized to better understand complex diseases such as cancer or neurodegenerative disorders?
- How might future developments in organoid technology influence personalized medicine approaches in clinical settings?
Key Findings
Research Background and Objectives
Organoids are three-dimensional (3D) cell cultures that mimic the architecture and functionality of real organs. This technology has emerged as a revolutionary tool in biomedical research, providing more physiologically relevant models than traditional two-dimensional (2D) cell cultures. The review discusses the history, development, strengths, limitations, and potential applications of organoids in various fields, including disease modeling, drug discovery, and regenerative medicine.
Main Methods/Materials/Experimental Design
Organoids can be derived from different types of stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells (ASCs). The generation of organoids involves culturing these stem cells in a defined 3D environment, often using extracellular matrix (ECM) components like Matrigel to provide structural support and signaling cues.
Process Flow of Organoid Generation
Key Results and Findings
- Organoid Development: The review highlights various organoid types, including gastrointestinal, liver, pancreatic, brain, and retinal organoids, showcasing their ability to replicate the architecture and functionality of their respective tissues.
- Disease Modeling: Patient-derived organoids have been successfully used to model genetic diseases (e.g., cystic fibrosis, microcephaly) and infectious diseases (e.g., Zika virus).
- Cancer Research: Organoids derived from tumors maintain the heterogeneity and architecture of the original tumors, allowing for better modeling of cancer biology and drug responses.
Main Conclusions/Significance/Innovation
Organoid technology represents a significant advancement in the field of biomedical research, offering a more accurate and versatile platform for studying human biology and disease. The ability to create patient-specific organoids holds promise for personalized medicine, allowing for tailored treatment strategies based on individual tumor responses. Additionally, organoids can facilitate drug discovery by providing a reliable system for high-throughput screening.
Research Limitations and Future Directions
While organoids provide numerous advantages, there are limitations:
- Microenvironment: Most organoids lack the full tumor microenvironment, which may affect their predictive power in clinical settings.
- Scalability: The complexity of 3D cultures makes scaling up for large studies challenging.
- Standardization: There is a need for standardized protocols to ensure consistency and reproducibility across different studies.
Future research should focus on improving organoid models by incorporating stromal and immune cells to better mimic the in vivo environment, as well as exploring the integration of organoid technology with other innovative platforms like organ-on-a-chip systems for enhanced physiological relevance.
Summary Table: Comparison of Organoid Applications
| Application Area | Description | Examples |
|---|---|---|
| Disease Modeling | Recapitulates disease mechanisms in vitro | Cystic fibrosis, cancer |
| Drug Discovery | Evaluates drug responses and toxicity | Chemotherapy, targeted therapies |
| Regenerative Medicine | Potential for organ replacement therapies | Intestinal and liver organoids |
| Precision Medicine | Tailors treatments based on individual responses | Patient-derived organoids |
| Toxicology Studies | Assesses drug safety and efficacy | Hepatic and renal toxicity tests |
In summary, organoid technology is transforming the landscape of biomedical research, providing innovative solutions for understanding human development, disease, and treatment strategies.
References
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Literatures Citing This Work
- An American Physiological Society cross-journal Call for Papers on "Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models". - Josephine C Adams;P Darwin Bell;Sue C Bodine;Heddwen L Brooks;Nigel Bunnett;Bina Joe;Kara Hansell Keehan;Thomas R Kleyman;André Marette;Rory E Morty;Jan-Marino Ramírez;Morten B Thomsen;Bill J Yates;Irving H Zucker - American journal of physiology. Lung cellular and molecular physiology (2020)
- A Review on the Current Knowledge on ZIKV Infection and the Interest of Organoids and Nanotechnology on Development of Effective Therapies against Zika Infection. - Samanta Gasco;María Ángeles Muñoz-Fernández - International journal of molecular sciences (2020)
- 3D Cell Cultures as Prospective Models to Study Extracellular Vesicles in Cancer. - Guillermo Bordanaba-Florit;Iratxe Madarieta;Beatriz Olalde;Juan M Falcón-Pérez;Félix Royo - Cancers (2021)
- Organoid research in digestive system tumors. - Xiaoxiao Yang;Xuewen Xu;Haitao Zhu;Ming Wang;Dongqing Wang - Oncology letters (2021)
- Cultures and cures: neurodiversity and brain organoids. - Andrew J Barnhart;Kris Dierickx - BMC medical ethics (2021)
- Patient-Derived Cancer Organoids for Precision Oncology Treatment. - Mark N Pernik;Cylaina E Bird;Jeffrey I Traylor;Diana D Shi;Timothy E Richardson;Samuel K McBrayer;Kalil G Abdullah - Journal of personalized medicine (2021)
- The Application of the Tissue Microarray (TMA) Technology to Analyze Cerebral Organoids. - Ida Biunno;Emanuela Paiola;Pasquale De Blasio - The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (2021)
- The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update. - Joseph Azar;Hisham F Bahmad;Darine Daher;Maya M Moubarak;Ola Hadadeh;Alissar Monzer;Samar Al Bitar;Mohamed Jamal;Mohamed Al-Sayegh;Wassim Abou-Kheir - International journal of molecular sciences (2021)
- In Vitro Strategies to Vascularize 3D Physiologically Relevant Models. - Alessandra Dellaquila;Chau Le Bao;Didier Letourneur;Teresa Simon-Yarza - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
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