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Feature Papers in Organoids
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Feature Papers in Organoids

A special issue of Organoids (ISSN 2674-1172).

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 42789

Special Issue Editors

Prof. Dr. Stefan Liebau

E-Mail Website
Guest Editor
Institute of Neuroanatomy & Developmental Biology INDB, Eberhard Karls University Tübingen, Österbergstr. 3, 72074 Tubingen, Germany
Interests: pluripotent stem cells; neurosensory systems; stem cell differentiation; neuroplasticity; neurogenesis; retinal organoids; gene therapy; organ-on-chip
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Bahram Parvin

E-Mail Website
Guest Editor
Department of Biomedical Engineering, University of Nevada, Reno, NV 89557, USA
Interests: high content screening of organoid models; tumor-stroma interactions
Prof. Dr. Süleyman Ergün

E-Mail Website
Guest Editor
Institute of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany
Interests: vascular morphogenesis; endothelial barrier function angiogenesis; vasculogenesis; tumor vascularization; vascular stem cells; adult stem cells; cardiovascular regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of “Feature Papers in Organoids” will be published in Organoids (ISSN 2674-1172), and is dedicated to the publication and discussion of research articles, reviews, and communications on all aspects of organoid development and technological advancements towards applications in tissue engineering, model organ development and biomedicine. We welcome reviews and outstanding articles to this Special Issue in order to improve the current knowledge on organoids. The scope of this Special Issue includes, but is not limited to, the following:

  • Organoid architecture;
  • Organoids in cell biology;
  • Organoids in tissue engineering;
  • Organoids in developmental biology;
  • Organoids in gene therapy and regenerative medicine;
  • Organoids in cancer research and drug screening;
  • Organoids in toxicology testing;
  • Model of bacteria and virus infection;
  • Modeling organ development and disease.

Prof. Dr. Stefan Liebau
Prof. Dr. Bahram Parvin
Prof. Dr. Süleyman Ergün
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Organoids is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • organoids
  • organ-on-chip
  • organ-on-a-chip
  • 3D cell culture
  • 3D organ model

Published Papers (7 papers)

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Research

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17 pages, 3582 KiB  
Article
Defined, Simplified, Scalable, and Clinically Compatible Hydrogel-Based Production of Human Brain Organoids
by Eva Tomaskovic-Crook, Sarah Liza Higginbottom, Binbin Zhang, Justin Bourke, Gordon George Wallace and Jeremy Micah Crook
Organoids 2023, 2(1), 20-36; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids2010002 - 11 Jan 2023
Cited by 4 | Viewed by 3991
Abstract
Human brain organoids present a new paradigm for modeling human brain organogenesis, providing unprecedented insight to the molecular and cellular processes of brain development and maturation. Other potential applications include in vitro models of disease and tissue trauma, as well as three-dimensional (3D) [...] Read more.
Human brain organoids present a new paradigm for modeling human brain organogenesis, providing unprecedented insight to the molecular and cellular processes of brain development and maturation. Other potential applications include in vitro models of disease and tissue trauma, as well as three-dimensional (3D) clinically relevant tissues for pharmaceuticals development and cell or tissue replacement. A key requirement for this emerging technology in both research and medicine is the simple, scalable, and reproducible generation of organoids using reliable, economical, and high-throughput culture platforms. Here we describe such a platform using a defined, clinically compliant, and readily available hydrogel generated from gelatin methacrylate (GelMA). We demonstrate the efficient production of organoids on GelMA from human induced pluripotent stem cells (iPSCs), with scalable production attained using 3D printed GelMA-based multiwell arrays. The differentiation of iPSCs was systematic, rapid, and direct to enable iPSCs to form organoids in their original position following seeding on GelMA, thereby avoiding further cell and organoid disruption. Early neural precursors formed by day 5, neural rosettes and early-stage neurons by day 14, and organoids with cellular and regional heterogeneity, including mature and electrophysiologically active neurons, by day 28. The optimised method provides a simplified and well-defined platform for both research and translation of iPSCs and derivative brain organoids, enabling reliable 3D in vitro modelling and experimentation, as well as the provision of clinically relevant cells and tissues for future therapeutics. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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13 pages, 2726 KiB  
Article
A Blood Vessel Organoid Model Recapitulating Aspects of Vasculogenesis, Angiogenesis and Vessel Wall Maturation
by Sven Schmidt, Yvonne Alt, Nikita Deoghare, Sarah Krüger, Anna Kern, Anna Frederike Rockel, Nicole Wagner, Süleyman Ergün and Philipp Wörsdörfer
Organoids 2022, 1(1), 41-53; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids1010005 - 28 Apr 2022
Cited by 10 | Viewed by 7632
Abstract
Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer [...] Read more.
Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5–6. Induced by VEGF application, CD31+ vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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Review

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19 pages, 4088 KiB  
Review
3D Tumor Spheroid and Organoid to Model Tumor Microenvironment for Cancer Immunotherapy
by Yichen Zhu, Elliot Kang, Matthew Wilson, Taylor Basso, Evelynn Chen, Yanqi Yu and Yan-Ruide Li
Organoids 2022, 1(2), 149-167; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids1020012 - 05 Dec 2022
Cited by 13 | Viewed by 7547
Abstract
The intricate microenvironment in which malignant cells reside is essential for the progression of tumor growth. Both the physical and biochemical features of the tumor microenvironment (TME) play a critical role in promoting the differentiation, proliferation, invasion, and metastasis of cancer cells. It [...] Read more.
The intricate microenvironment in which malignant cells reside is essential for the progression of tumor growth. Both the physical and biochemical features of the tumor microenvironment (TME) play a critical role in promoting the differentiation, proliferation, invasion, and metastasis of cancer cells. It is therefore essential to understand how malignant cells interact and communicate with an assortment of supportive tumor-associated cells including macrophages, fibroblasts, endothelial cells, and other immune cells. To study the complex mechanisms behind cancer progression, 3D spheroid and organoid models are widely in favor because they replicate the stromal environment and multicellular structure present within an in vivo tumor. It provides more precise data about the cell–cell interactions, tumor characteristics, drug discovery, and metabolic profile of cancer cells compared to oversimplified 2D systems and unrepresentative animal models. This review provides a description of the key elements of the tumor microenvironment as well as early research using cell-line derived, 3D spheroid tumor models that paved the way for the adoption of patient-derived spheroid and organoid models. In particular, 3D spheroid and organoid models provide a method for drug screening with a particular emphasis on influence of the TME in cancer immunotherapy. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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21 pages, 2167 KiB  
Review
Metabolic Studies in Organoids: Current Applications, Opportunities and Challenges
by Elena Richiardone, Valentin Van den Bossche and Cyril Corbet
Organoids 2022, 1(1), 85-105; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids1010008 - 13 Jun 2022
Cited by 8 | Viewed by 6433
Abstract
Organoid technologies represent a major breakthrough in biomedical research since they offer increasingly sophisticated models for studying biological mechanisms supporting human development and disease. Organoids are three-dimensional (3D) physiological in vitro systems that recapitulate the genetic, histological and functional features of the in [...] Read more.
Organoid technologies represent a major breakthrough in biomedical research since they offer increasingly sophisticated models for studying biological mechanisms supporting human development and disease. Organoids are three-dimensional (3D) physiological in vitro systems that recapitulate the genetic, histological and functional features of the in vivo tissues of origin more accurately than classical cell culture methods. In the last decade, organoids have been derived from various healthy and diseased tissues and used for a wide range of applications in basic and translational research, including (cancer) tissue biology, development, regeneration, disease modeling, precision medicine, gene editing, biobanking and drug screening. Here, we report the current applications of organoid models to study (stem) cell metabolism in several pathophysiological contexts such as cancer and metabolic diseases. More precisely, we discuss the relevance and limitations of these 3D cultures to model and study metabolic (dys)functions associated with hepatic, renal or pancreatic disorders, as well as tumor development and progression. We also describe the use of organoids to understand the dynamic interaction between diet, microbiota and the intestinal epithelium. Finally, this review explores recent methodological improvements in organoid culture that may help to better integrate the influence of microenvironmental conditions in the study of tumor cell metabolic phenotypes. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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9 pages, 1096 KiB  
Review
Organoids as Miniature Twins—Challenges for Comparability and Need for Data Standardization and Access
by Antonie Fuhr, Andreas Kurtz, Christian Hiepen and Sabine Müller
Organoids 2022, 1(1), 28-36; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids1010003 - 09 Apr 2022
Cited by 4 | Viewed by 2754
Abstract
Organoids derived from human stem cell lines represent genetically mostly identical models of their donors. Their use as personalized in vitro miniature twins of living individuals creates challenges of reproducibility, comparability and standardization. To fully exploit personalization, it is essential to assess individual [...] Read more.
Organoids derived from human stem cell lines represent genetically mostly identical models of their donors. Their use as personalized in vitro miniature twins of living individuals creates challenges of reproducibility, comparability and standardization. To fully exploit personalization, it is essential to assess individual variabilities in organoid function, morphology or maturity. There is a need to establish platforms to compare individual organoids and to link them to data elements related to the individual donor. Moreover, principal ethical issues arise because of their infinite repetition for an unlimited period of time and global dissemination. This infinite temporal and spatial space applies to the biological material but also to the data associated with it. It increases the possibility of uses that are unpredictable at the time of donation, and thus, beyond the donor’s consented choices. We propose an open data platform to address the issue of authenticity and persistent comparability of the biological organoid models, and of preserving the ethical provenance information. The platform would collect standardized donors, organoids and ethical information to create a system suitable for quality control of individual organoids. We discuss whether the human pluripotent stem cell registry (hPSCreg), a well-established resource for stem cell data, provides a suitable model platform. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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26 pages, 3370 KiB  
Review
Organoid Models of SARS-CoV-2 Infection: What Have We Learned about COVID-19?
by Bang M. Tran, Georgia Deliyannis, Abderrahman Hachani, Linda Earnest, Joseph Torresi and Elizabeth Vincan
Organoids 2022, 1(1), 2-27; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids1010002 - 02 Mar 2022
Cited by 10 | Viewed by 7234
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which was classified as a pandemic in March 2020. As of 22 January 2022, globally more than 347 million cases of COVID-19 have been diagnosed, with 5.6 million deaths, making it [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which was classified as a pandemic in March 2020. As of 22 January 2022, globally more than 347 million cases of COVID-19 have been diagnosed, with 5.6 million deaths, making it the deadliest pandemic since the influenza pandemic in 1918. The clinical presentation of COVID-19-related illness spans from asymptomatic to mild respiratory symptoms akin to influenza infection to acute symptoms, including pneumonia necessitating hospitalisation and admission to intensive care units. COVID-19 starts in the upper respiratory tract and lungs but in severe cases can also involve the heart, blood vessels, brain, liver, kidneys and intestine. The increasing global health and economic burden of COVID-19 necessitates an urgent and global response. Understanding the functional characteristics and cellular tropism of SARS-CoV-2, and the pathogenesis that leads to multi-organ failure and death, has prompted an unprecedented adoption of organoid models. Successful drug discovery and vaccine development rely on pre-clinical models that faithfully recapitulate the viral life cycle and the host cell response to infection. Human stem cell-derived organoids fulfill these criteria. Here we highlight the role of organoids in the study of SARS-CoV-2 infection and modelling of COVID-19 pathogenesis. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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Other

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16 pages, 3036 KiB  
Perspective
Human Brain Organoids and Consciousness: Moral Claims and Epistemic Uncertainty
by Eliza Goddard, Eva Tomaskovic-Crook, Jeremy Micah Crook and Susan Dodds
Organoids 2023, 2(1), 50-65; https://0-doi-org.brum.beds.ac.uk/10.3390/organoids2010004 - 07 Feb 2023
Cited by 5 | Viewed by 5329
Abstract
Human brain organoids provide a remarkable opportunity to model prenatal human brain biology in vitro by recapitulating features of in utero molecular, cellular and systems biology. An ethical concern peculiar to human brain organoids is whether they are or could become capable of [...] Read more.
Human brain organoids provide a remarkable opportunity to model prenatal human brain biology in vitro by recapitulating features of in utero molecular, cellular and systems biology. An ethical concern peculiar to human brain organoids is whether they are or could become capable of supporting sentience through the experience of pain or pleasure and/or consciousness, including higher cognitive abilities such as self-awareness. Identifying the presence of these traits is complicated by several factors, beginning with consciousness—which is a highly contested concept among neuroscientists, cognitive scientists, and philosophers and so there is no agreed definition. Secondly, given human brain organoids are disembodied, there is no practical way to identify evidence of consciousness as we might in humans or animals. What would count as evidence of organoid consciousness is an emerging area of research. To address concerns about consciousness and human brain organoids, in this paper we clarify the morally relevant aspects of human consciousness, phenomenal experience and embodied development and explore the empirical basis of consciousness to develop a defensible framework for informed decision-making on the moral significance and utility of brain organoids, which can also guide regulation and future research of these novel biological systems. Full article
(This article belongs to the Special Issue Feature Papers in Organoids)
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