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Curated Papers > Recent high-impact research on "organoids" (IF≥30, last 5 years)

Organoids by design. ​

Literature Information ​

DOI10.1126/science.aaw7567
PMID31171692
JournalScience (New York, N.Y.)
Impact Factor45.8
JCR QuartileQ1
Publication Year2019
Times Cited170
KeywordsOrganoids, Cellular Complexity, Tissue Function, Engineering Design
Literature TypeJournal Article
ISSN0036-8075
Pages956-959
Issue364(6444)
AuthorsTakanori Takebe, James M Wells

TL;DR ​

This research explores the advancement of organoids, which are multicellular structures derived from adult organs or pluripotent stem cells, aiming to enhance their cellular complexity and functional organization through engineering approaches inspired by embryonic development. The findings highlight the potential for creating next-generation organoids with improved tissue complexity and functionality, which could significantly contribute to regenerative medicine and disease modeling.

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Organoids · Cellular Complexity · Tissue Function · Engineering Design

Abstract ​

Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions of organoids range from simple epithelial structures to complex, disorganized tissues with large cellular diversity. The current challenge is to engineer cellular complexity into organoids in a controlled manner that results in organized assembly and acquisition of tissue function. These efforts have relied on studies of organ assembly during embryonic development and have resulted in the development of organoids with multilayer tissue complexity and higher-order functions. We discuss how the next generation of organoids can be designed by means of an engineering-based narrative design to control patterning, assembly, morphogenesis, growth, and function.

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Primary Questions Addressed ​

  1. How can the engineering principles applied in organoid design enhance their functionality compared to traditional organoid methods?
  2. What specific challenges are faced when trying to replicate the cellular diversity found in natural organs within engineered organoids?
  3. In what ways can insights from embryonic development inform the design of more complex organoids with specific tissue functions?
  4. How might advancements in organoid technology impact drug testing and personalized medicine in the future?
  5. What are the ethical considerations surrounding the use of engineered organoids in research and therapy?

Key Findings ​

Research Background and Purpose ​

Organoids are three-dimensional (3D) multicellular structures derived from adult organs or pluripotent stem cells (PSCs). They serve as valuable models for studying organ development, disease mechanisms, and drug testing. The current challenge in organoid research is to engineer these structures with controlled cellular complexity and functionality, mimicking natural organogenesis. This review discusses the application of engineering principles to enhance organoid design, focusing on aspects like patterning, assembly, and function.

Main Methods/Materials/Experimental Design ​

The authors propose a framework called "narrative engineering," which combines biological and engineering principles to direct organoidgenesis. The process can be illustrated as follows:

Mermaid diagram

  • Space Design: Utilizes homogeneous and heterogeneous aggregates to facilitate self-organization. Homogeneous aggregates initiate tissue self-organization, while heterogeneous aggregates combine multiple progenitor types to enhance functional complexity.

  • Biological Environmental Control: Involves the use of soluble factors and extracellular matrices to recapitulate organogenesis mechanisms. This includes manipulating matrix composition and stiffness to drive organoid formation.

  • Synthetic Environmental Control: Applies engineered systems to modulate cell properties, nutrient flow, and mechanical forces to enhance organoid growth and maturation.

Key Results and Findings ​

  1. Enhanced Complexity: Organoids can incorporate critical cell types such as blood vessels, nerves, and immune cells, allowing for more realistic tissue models.
  2. Functionality: Organoids have demonstrated various functions, including muscle contractility and insulin secretion, but often lack full adult functionality.
  3. Maturation: Prolonged culture time improves organoid maturity, and engrafting organoids onto vascular beds in vivo promotes growth and functionality.

Main Conclusions/Significance/Innovation ​

The integration of engineering principles with biological understanding can significantly advance organoid technology. By controlling the processes of organogenesis, researchers can create organoids that are not only structurally complex but also functionally mature. This approach opens new avenues for studying human development, disease modeling, and regenerative medicine, potentially leading to breakthroughs in organ transplantation and drug development.

Research Limitations and Future Directions ​

  • Limitations: Current organoids often do not fully replicate adult organ functionality and are limited in size due to diffusion constraints. Additionally, achieving reproducibility and scalability in organoid production remains a challenge.
  • Future Directions: The authors suggest further exploration of narrative engineering principles to refine organoid complexity and functionality. Future research should focus on optimizing environmental controls and integrating advanced biotechnological tools, such as gene editing and microfluidics, to enhance organoid applications in research and therapy.

References ​

  1. Overview of Lung Development in the Newborn Human. - David Warburton - Neonatology (2017)
  2. Apoptotic force and tissue dynamics during Drosophila embryogenesis. - Yusuke Toyama;Xomalin G Peralta;Adrienne R Wells;Daniel P Kiehart;Glenn S Edwards - Science (New York, N.Y.) (2008)
  3. Fused cerebral organoids model interactions between brain regions. - Joshua A Bagley;Daniel Reumann;Shan Bian;Julie Lévi-Strauss;Juergen A Knoblich - Nature methods (2017)
  4. Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres. - Celina Monteiro Abreu;Lucio Gama;Susanne Krasemann;Megan Chesnut;Shelly Odwin-Dacosta;Helena T Hogberg;Thomas Hartung;David Pamies - Frontiers in microbiology (2018)
  5. Tissue engineering. - R Langer;J P Vacanti - Science (New York, N.Y.) (1993)
  6. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. - Toshiro Sato;Hans Clevers - Science (New York, N.Y.) (2013)
  7. Microglia innately develop within cerebral organoids. - Paul R Ormel;Renata Vieira de Sá;Emma J van Bodegraven;Henk Karst;Oliver Harschnitz;Marjolein A M Sneeboer;Lill Eva Johansen;Roland E van Dijk;Nicky Scheefhals;Amber Berdenis van Berlekom;Eduardo Ribes Martínez;Sandra Kling;Harold D MacGillavry;Leonard H van den Berg;René S Kahn;Elly M Hol;Lot D de Witte;R Jeroen Pasterkamp - Nature communications (2018)
  8. Molecular control of macroscopic forces drives formation of the vertebrate hindgut. - Nandan L Nerurkar;ChangHee Lee;L Mahadevan;Clifford J Tabin - Nature (2019)
  9. Blueprint for an intestinal villus: Species-specific assembly required. - Katherine D Walton;Darcy Mishkind;Misty R Riddle;Clifford J Tabin;Deborah L Gumucio - Wiley interdisciplinary reviews. Developmental biology (2018)
  10. Modelling cancer in microfluidic human organs-on-chips. - Alexandra Sontheimer-Phelps;Bryan A Hassell;Donald E Ingber - Nature reviews. Cancer (2019)

Literatures Citing This Work ​

  1. Pluripotent stem cell-derived organogenesis in the rat model system. - Masumi Hirabayashi;Teppei Goto;Shinichi Hochi - Transgenic research (2019)
  2. Building Complex Life Through Self-Organization. - Mireille M J P E Sthijns;Vanessa L S LaPointe;Clemens A van Blitterswijk - Tissue engineering. Part A (2019)
  3. 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)
  4. Organoids - New Models for Host-Helminth Interactions. - María A Duque-Correa;Rick M Maizels;Richard K Grencis;Matthew Berriman - Trends in parasitology (2020)
  5. De Novo-Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids, and in Vivo. - Hongbao Fang;Shankun Yao;Qixin Chen;Chunyan Liu;Yuqi Cai;Shanshan Geng;Yang Bai;Zhiqi Tian;Amanda L Zacharias;Takanori Takebe;Yuncong Chen;Zijian Guo;Weijiang He;Jiajie Diao - ACS nano (2019)
  6. Novel three-dimensional cultures provide insights into thyroid cancer behavior. - Mason A Lee;Kensey N Bergdorf;Courtney J Phifer;Caroline Y Jones;Sonia Y Byon;Leah M Sawyer;Joshua A Bauer;Vivian L Weiss - Endocrine-related cancer (2020)
  7. Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications. - Daniel Fan;Urs Staufer;Angelo Accardo - Bioengineering (Basel, Switzerland) (2019)
  8. Liver Buds and Liver Organoids: New Tools for Liver Development, Disease and Medical Application. - Fanhong Zeng;Yue Zhang;Xu Han;Jun Weng;Yi Gao - Stem cell reviews and reports (2019)
  9. Bioengineered microenvironment to culture early embryos. - Zhen Gu;Jia Guo;Hongmei Wang;Yongqiang Wen;Qi Gu - Cell proliferation (2020)
  10. Engineering Tissue Fabrication With Machine Intelligence: Generating a Blueprint for Regeneration. - Joohyun Kim;Jane A McKee;Jake J Fontenot;Jangwook P Jung - Frontiers in bioengineering and biotechnology (2019)

... (160 more literatures)

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