Curated Papers > In recent years, high-impact research on "organoids" (Impact Factor ≥ 30, within the last 5 years)

Engineering organoids.

Literature Information

DOI	10.1038/s41578-021-00279-y
PMID	33623712
Journal	Nature reviews. Materials
Impact Factor	86.2
JCR Quartile	Q1
Publication Year	2021
Times Cited	444
Keywords	Morphogenesis, Organogenesis, Stem cells, Tissue engineering
Literature Type	Journal Article, Review
ISSN	2058-8437
Pages	402-420
Issue	6(5)
Authors	Moritz Hofer, Matthias P Lutolf

TL;DR

This review highlights the potential of engineering approaches to overcome limitations in traditional organoid culture, such as high variability and restricted access, which hinder their application in personalized medicine and drug screening. By integrating cell surface and genetic engineering, stem cell niche design, and microfluidic systems, the study demonstrates how these innovations can enhance reproducibility and control in organoid systems, facilitating their clinical translation.

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Morphogenesis · Organogenesis · Stem cells · Tissue engineering

Abstract

Organoids are in vitro miniaturized and simplified model systems of organs that have gained enormous interest for modelling tissue development and disease, and for personalized medicine, drug screening and cell therapy. Despite considerable success in culturing physiologically relevant organoids, challenges remain to achieve real-life applications. In particular, the high variability of self-organizing growth and restricted experimental and analytical access hamper the translatability of organoid systems. In this Review, we argue that many limitations of traditional organoid culture can be addressed by engineering approaches at all levels of organoid systems. We investigate cell surface and genetic engineering approaches, and discuss stem cell niche engineering based on the design of matrices that allow spatiotemporal control of organoid growth and shape-guided morphogenesis. We examine how microfluidic approaches and lessons learnt from organs-on-a-chip enable the integration of mechano-physiological parameters and increase accessibility of organoids to improve functional readouts. Applying engineering principles to organoids increases reproducibility and provides experimental control, which will, ultimately, be required to enable clinical translation.

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Primary Questions Addressed

1. What specific engineering techniques can be employed to reduce the variability in self-organizing growth of organoids?
2. How do genetic engineering approaches influence the functional characteristics of organoids in disease modeling?
3. In what ways can the design of matrices enhance spatiotemporal control in organoid culture?
4. What role do microfluidic systems play in improving the accessibility and functionality of organoids for drug screening?
5. How can the integration of mechano-physiological parameters through engineering enhance the translational potential of organoids in personalized medicine?

Key Findings

Research Background and Purpose

Organoids are miniaturized, simplified models of organs developed in vitro, gaining traction for applications in modeling tissue development, disease, personalized medicine, drug screening, and cell therapy. Despite advancements, the variability in organoid growth and limited experimental access pose challenges for clinical translation. This review discusses how engineering approaches can address these limitations across different levels of organoid systems.

Main Methods/Materials/Experimental Design

The authors propose a comprehensive engineering strategy involving:

1. Cell Engineering: Modifying cell surfaces and using genetic engineering to enhance organoid robustness and functionality.
2. Niche Engineering: Designing matrices that mimic the stem cell niche to control organoid growth and morphogenesis.
3. Microfluidic Approaches: Integrating mechano-physiological parameters and improving organoid accessibility for better functional readouts.

The engineering strategies are summarized in the following flowchart:

Key Results and Findings

• Increased Reproducibility: Engineering strategies enhance the consistency of organoid formation and functionality.
• Enhanced Functionality: Organoids engineered to better mimic physiological conditions show improved metabolic functions and cellular diversity.
• Applications in Disease Modeling: Patient-derived organoids can accurately model diseases, providing insights into personalized treatment options.

Main Conclusions/Significance/Innovation

The integration of engineering principles into organoid development offers a pathway to enhance their clinical applicability. By addressing issues such as growth variability and functional limitations, engineered organoids can provide more reliable models for disease research and therapeutic applications. This innovative approach can potentially transform organoid technology into a cornerstone of personalized medicine.

Research Limitations and Future Directions

• Current Limitations: Organoids still face challenges related to limited lifespan, accessibility for experimentation, and the need for more sophisticated readouts.
• Future Directions: Emphasis on multi-organ systems and the incorporation of immune components could further enhance the physiological relevance of organoids. Development of high-throughput screening methods and automation in organoid culture is essential for advancing drug discovery and regenerative medicine.

Aspect	Current Limitations	Future Directions
Lifespan	Short lifespan of organoids	Development of long-lived organoid systems
Accessibility	Limited access for experimental manipulation	Microfluidic integration for better access
Functional Readouts	Reliance on basic morphological assessments	Advanced biosensing and imaging techniques
Multi-organ Interactions	Lack of integration between different organoid types	Engineering multi-organ systems for complex interactions

In conclusion, the engineering of organoids represents a promising avenue to overcome existing challenges, making them more suitable for clinical applications and advancing our understanding of human biology and disease.

References

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Literatures Citing This Work

1. Heart organoids and tissue models for modeling development and disease. - Matthew Miyamoto;Lucy Nam;Suraj Kannan;Chulan Kwon - Seminars in cell & developmental biology (2021)
2. Of form and function: Early cardiac morphogenesis across classical and emerging model systems. - Bhavana Shewale;Nicole Dubois - Seminars in cell & developmental biology (2021)
3. Next-Generation Human Liver Models for Antimalarial Drug Assays. - Kasem Kulkeaw - Antibiotics (Basel, Switzerland) (2021)
4. Harnessing organs-on-a-chip to model tissue regeneration. - Daniel Naveed Tavakol;Sharon Fleischer;Gordana Vunjak-Novakovic - Cell stem cell (2021)
5. Cancer spheroids derived exosomes reveal more molecular features relevant to progressed cancer. - Junfang Tu;Xun Luo;Haitao Liu;Jifeng Zhang;Mei He - Biochemistry and biophysics reports (2021)
6. The role of physical cues in the development of stem cell-derived organoids. - Ilaria Tortorella;Chiara Argentati;Carla Emiliani;Sabata Martino;Francesco Morena - European biophysics journal : EBJ (2022)
7. Successful Patient-Derived Organoid Culture of Gynecologic Cancers for Disease Modeling and Drug Sensitivity Testing. - Jianling Bi;Andreea M Newtson;Yuping Zhang;Eric J Devor;Megan I Samuelson;Kristina W Thiel;Kimberly K Leslie - Cancers (2021)
8. Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development. - Lucie Zilova;Venera Weinhardt;Tinatini Tavhelidse;Christina Schlagheck;Thomas Thumberger;Joachim Wittbrodt - eLife (2021)
9. Operationalizing the Use of Biofabricated Tissue Models as Preclinical Screening Platforms for Drug Discovery and Development. - Olive Jung;Min Jae Song;Marc Ferrer - SLAS discovery : advancing life sciences R & D (2021)
10. Changes in Stem Cell Regulation and Epithelial Organisation during Carcinogenesis and Disease Progression in Gynaecological Malignancies. - Paula Cunnea;Christina Fotopoulou;Jennifer Ploski;Fabian Trillsch;Sven Mahner;Mirjana Kessler - Cancers (2021)

... (434 more literatures)

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