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Organoids-on-a-chip.
Literature Information
| DOI | 10.1126/science.aaw7894 |
|---|---|
| PMID | 31171693 |
| Journal | Science (New York, N.Y.) |
| Impact Factor | 45.8 |
| JCR Quartile | Q1 |
| Publication Year | 2019 |
| Times Cited | 361 |
| Keywords | Organoids, Chip Technology, Biomedicine, Microenvironment, Engineering Approaches |
| Literature Type | Journal Article |
| ISSN | 0036-8075 |
| Pages | 960-965 |
| Issue | 364(6444) |
| Authors | Sunghee Estelle Park, Andrei Georgescu, Dongeun Huh |
TL;DR
This review highlights the potential of organ-on-a-chip technology to enhance the production, control, and analysis of stem cell-derived organoids that mimic the structure and function of real organs, addressing significant challenges in organoid research. By exploring innovative engineering approaches, the study underscores the importance of integrating this technology to advance biomedicine and overcome existing limitations in organoid applications.
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Organoids · Chip Technology · Biomedicine · Microenvironment · Engineering Approaches
Abstract
Recent studies have demonstrated an array of stem cell-derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology.
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Primary Questions Addressed
- How can organ-on-a-chip technology enhance the study of organoid behavior under different physiological conditions?
- What specific engineering approaches are currently being developed to improve the production of organoids on a chip?
- In what ways can organoid-on-a-chip systems be utilized to model disease processes more accurately than traditional methods?
- What are the potential applications of organoids-on-a-chip in drug testing and personalized medicine?
- How do the microenvironmental factors within organ-on-a-chip systems influence the development and functionality of organoids?
Key Findings
Research Background and Purpose
Organoids, derived from stem cells, are miniature organs that replicate the structural and functional characteristics of their in vivo counterparts. Despite their potential, traditional organoid culture methods face limitations in controlling their microenvironment, which hinders their development and reproducibility. This review explores the integration of organ-on-a-chip technology with organoid research to address these challenges and enhance the capabilities of organoids for biomedical applications.
Main Methods/Materials/Experimental Design
The review discusses the principles and designs of organ-on-a-chip systems, which are microfabricated devices that simulate the functional units of human organs. The construction process includes:
- Reductionist Analysis: Understanding the anatomy of the target organ to identify essential elements for physiological function.
- Microfabrication Techniques: Using methods like soft lithography to create devices that mimic the identified organ features.
- Microenvironment Control: Employing microfluidic systems to manage biochemical gradients, nutrient supply, and mechanical forces.
Key Results and Findings
- Microenvironmental Control: Organ-on-a-chip technology allows for precise control over biochemical gradients and nutrient supply, enhancing organoid development.
- Tissue-Tissue Interactions: Coculture systems can recreate interactions between different tissue types, improving organoid maturity and function.
- Multiorgan Systems: Integrating multiple organoids in a single platform enables the simulation of complex physiological interactions, which is crucial for drug testing and understanding disease mechanisms.
Main Conclusions/Significance/Innovation
The integration of organoids with organ-on-a-chip technology represents a significant advancement in biomedical research. This approach not only enhances the physiological relevance of organoid models but also facilitates high-throughput drug screening and personalized medicine applications. The review highlights the potential of these combined systems to create more predictive preclinical models and to improve the understanding of human physiology and disease.
Research Limitations and Future Directions
While organoids-on-a-chip show great promise, challenges remain, including:
- Dynamic Changes: Current models may not fully replicate the dynamic structural and functional changes during organ development.
- Material Limitations: The use of poorly defined materials like Matrigel can introduce variability in results.
- Complexity in Imaging: The three-dimensionality of organoids complicates imaging and analysis.
Future research should focus on developing new biomaterials, enhancing the dynamic capabilities of organoid models, and refining imaging techniques to fully leverage the potential of organoids-on-a-chip in regenerative medicine and drug discovery.
References
- Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. - Yu Shrike Zhang;Julio Aleman;Su Ryon Shin;Tugba Kilic;Duckjin Kim;Seyed Ali Mousavi Shaegh;Solange Massa;Reza Riahi;Sukyoung Chae;Ning Hu;Huseyin Avci;Weijia Zhang;Antonia Silvestri;Amir Sanati Nezhad;Ahmad Manbohi;Fabio De Ferrari;Alessandro Polini;Giovanni Calzone;Noor Shaikh;Parissa Alerasool;Erica Budina;Jian Kang;Nupura Bhise;João Ribas;Adel Pourmand;Aleksander Skardal;Thomas Shupe;Colin E Bishop;Mehmet Remzi Dokmeci;Anthony Atala;Ali Khademhosseini - Proceedings of the National Academy of Sciences of the United States of America (2017)
- Clarifying intact 3D tissues on a microfluidic chip for high-throughput structural analysis. - Yih Yang Chen;Pamuditha N Silva;Abdullah Muhammad Syed;Shrey Sindhwani;Jonathan V Rocheleau;Warren C W Chan - Proceedings of the National Academy of Sciences of the United States of America (2016)
- Microfluidic platforms for mechanobiology. - William J Polacheck;Ran Li;Sebastien G M Uzel;Roger D Kamm - Lab on a chip (2013)
- Advancing Intestinal Organoid Technology Toward Regenerative Medicine. - Tetsuya Nakamura;Toshiro Sato - Cellular and molecular gastroenterology and hepatology (2018)
- Human stomach-on-a-chip with luminal flow and peristaltic-like motility. - Kang Kug Lee;Heather A McCauley;Taylor R Broda;Matthew J Kofron;James M Wells;Christian I Hong - Lab on a chip (2018)
- Organs-on-a-chip: a new tool for drug discovery. - Alessandro Polini;Ljupcho Prodanov;Nupura S Bhise;Vijayan Manoharan;Mehmet R Dokmeci;Ali Khademhosseini - Expert opinion on drug discovery (2014)
- Physiologically relevant organs on chips. - Kyungsuk Yum;Soon Gweon Hong;Kevin E Healy;Luke P Lee - Biotechnology journal (2014)
- Next generation organoids for biomedical research and applications. - Yan-Ru Lou;Alan W Leung - Biotechnology advances (2018)
- Progress and potential in organoid research. - Giuliana Rossi;Andrea Manfrin;Matthias P Lutolf - Nature reviews. Genetics (2018)
- Guided self-organization and cortical plate formation in human brain organoids. - Madeline A Lancaster;Nina S Corsini;Simone Wolfinger;E Hilary Gustafson;Alex W Phillips;Thomas R Burkard;Tomoki Otani;Frederick J Livesey;Juergen A Knoblich - Nature biotechnology (2017)
Literatures Citing This Work
- Organoids by design. - Takanori Takebe;James M Wells - Science (New York, N.Y.) (2019)
- Mechanobiology of cells and cell systems, such as organoids. - Ece Bayir;Aylin Sendemir;Yannis F Missirlis - Biophysical reviews (2019)
- Past, Present, and Future of Brain Organoid Technology. - Bonsang Koo;Baekgyu Choi;Hoewon Park;Ki-Jun Yoon - Molecules and cells (2019)
- Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil. - Joseph Park;Sung Hoon Baik;Inhee Mook-Jung;Daniel Irimia;Hansang Cho - Frontiers in immunology (2019)
- Insight into Mechanobiology: How Stem Cells Feel Mechanical Forces and Orchestrate Biological Functions. - Chiara Argentati;Francesco Morena;Ilaria Tortorella;Martina Bazzucchi;Serena Porcellati;Carla Emiliani;Sabata Martino - International journal of molecular sciences (2019)
- Organs-on-Chips in Clinical Pharmacology: Putting the Patient Into the Center of Treatment Selection and Drug Development. - Richard W Peck;Christopher D Hinojosa;Geraldine A Hamilton - Clinical pharmacology and therapeutics (2020)
- Organoids - New Models for Host-Helminth Interactions. - María A Duque-Correa;Rick M Maizels;Richard K Grencis;Matthew Berriman - Trends in parasitology (2020)
- Recent Updates on Research Models and Tools to Study Virus-Host Interactions at the Placenta. - Jae Kyung Lee;Soo-Jin Oh;Hosun Park;Ok Sarah Shin - Viruses (2019)
- Emerging organoid models: leaping forward in cancer research. - Han Fan;Utkan Demirci;Pu Chen - Journal of hematology & oncology (2019)
- Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises. - Chiara Argentati;Ilaria Tortorella;Martina Bazzucchi;Francesco Morena;Sabata Martino - Journal of personalized medicine (2020)
... (351 more literatures)
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