Organoids: a systematic review of ethical issues

Jongh, Dide de; Massey, Emma K.; Berishvili, Ekaterine; Fonseca, Laura Mar; Lebreton, Fanny; Bellofatto, Kevin; Bignard, Juliette; Seißler, Jochen; Buerck, Leila Wolf-van; Honarpisheh, Mohsen; Zhang, Yichen; Lei, Yutian; Pehl, Monika; Follenzi, Antonia; Olgasi, Cristina; Cucci, Alessia; Borsotti, Chiara; Assanelli, Simone; Piemonti, Lorenzo; Citro, Antonio; Pellegrini, Silvia; Pignatelli, Cataldo; Campo, Francesco; Thaunat, Olivier; Cronin, Antonia; Mey, Devi; Parisotto, Chiara; Rossi, Giovanna; Kugelmeier, Patrick; Wolint, Petra; Muhlemann, M.F.; Pal-Kutas, Karolina; Cavallaro, Marco; Götz, Julia; Müller, Jeanette; Bunnik, Eline M.

doi:10.1186/s13287-022-02950-9

Cited by 76 publications

(53 citation statements)

References 122 publications

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“…In addition, important challenges remain in re-creating within multicellular systems the exact replicates of the in vivo tissue microenvironment, such as the tissue-tissue interface, spatiotemporal distribution of gases, nutrients and waste, and the mechanical microenvironment ( Duval et al, 2017 ). In most of the examples so far available, 3D multicellular systems better recapitulated early developmental states instead of mature adult phenotypes and show high between-batch heterogeneity ( de Jongh et al, 2022 ). This is due in part to the challenges of maintaining long-term cultures, with organoids forming necrotic cores due to a lack of nutrient permeability as they grow.…”

Section: Outlook and Future Perspectivesmentioning

confidence: 99%

“…Crucially, organoids are grown in an ECM which provides mechanical support to the cells. Organoids can be derived from various sources of mouse or human stem cells, including embryonic stem cells (ESCs), adult tissue-resident stem cells (AdSCs) and induced pluripotent stem cells (iPSCs) ( Camp et al, 2015 ; Knight and Przyborski, 2015 ; de Jongh et al, 2022 ; Morais et al, 2022 ). Hence, human organoids represent a powerful 3D multicellular system for modelling human-specific aspects of development and disease, bridging the gap between 2D cell culture methods and animal models ( Figure 1 and Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

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3D multicellular systems in disease modelling: From organoids to organ-on-chip

Goldrick

Guri

Herrera-Oropeza

et al. 2023

Front. Cell Dev. Biol.

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Cell-cell interactions underlay organ formation and function during homeostasis. Changes in communication between cells and their surrounding microenvironment are a feature of numerous human diseases, including metabolic disease and neurological disorders. In the past decade, cross-disciplinary research has been conducted to engineer novel synthetic multicellular organ systems in 3D, including organoids, assembloids, and organ-on-chip models. These model systems, composed of distinct cell types, satisfy the need for a better understanding of complex biological interactions and mechanisms underpinning diseases. In this review, we discuss the emerging field of building 3D multicellular systems and their application for modelling the cellular interactions at play in diseases. We report recent experimental and computational approaches for capturing cell-cell interactions as well as progress in bioengineering approaches for recapitulating these complexities ex vivo. Finally, we explore the value of developing such multicellular systems for modelling metabolic, intestinal, and neurological disorders as major examples of multisystemic diseases, we discuss the advantages and disadvantages of the different approaches and provide some recommendations for further advancing the field.

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Section: Outlook and Future Perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3D multicellular systems in disease modelling: From organoids to organ-on-chip

Goldrick

Guri

Herrera-Oropeza

et al. 2023

Front. Cell Dev. Biol.

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“…Cooperation between institutions is more domestic and less transnational. As this area of research involves national bioinformation security and many ethical issues [31,32], future research collaborations are likely to be concentrated within countries.…”

Section: Co-authorship and Top 10 In Uential Authorsmentioning

confidence: 99%

Research Trends in Lung Organoids: Bibliometric Analysis and Visualization

Peng

et al. 2023

Preprint

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Background Lung organoids have emerged as a promising tool for studying lung development, function, and disease pathology. The present study aimed to analyze the current status and development trends of lung organoid research over the past years, present visual representations, and provide references for future research directions using bibliometric analysis. Methods Information on articles on lung organoids extracted from the Web of Science Core Collection, such as year of publication, journal, country, institution, author, and keywords, was analyzed. R, VOSviewer, and SCImago Graphica were used to visualize publication trends, co-authorship analysis, co-occurrence analysis, and hotspot evolution. Results The number of global publications has increased from 1 in 2011 to 512 in 2022. The cell produced the highest number of citations (2,069 citations). The United States (6,694 citations and 177 publications), University Medical Center Utrecht (2,060 citations and 9 publications), and Clevers H (2,570 citations and 15 publications) were the most influential countries, institutions, and authors, respectively. Co-occurrence cluster analysis of the top 54 keywords formed four clusters: (1) pulmonary fibrosis (PF), (2) lung cancer, (3) cystic fibrosis (CF), (4) coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusion Organoid technology undoubtedly played an important role in the study of COVID-19, but with the passing of the COVID-19 epidemic, the research focus may return to refractory lung diseases such as PF, CF, and lung cancer. Standardized culture, living biobanks, and multimodal model systems for lung disease may be the future research directions in the field of lung organoids.

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“…For instance, the transplantation of organoids in rodent brains has raised some concerns as to how a juncture would be treated as a human–rodent mixture, legally and ethically [ 137 , 138 ]. Recently, a systematic review of ethical issues has been presented [ 139 ] to assist in the responsible development and clinical implementation of human brain organoids. A four-step approach has been proposed to assist in overcoming ethical and legal concerns related to the generation and application of organoids [ 140 ].…”

Section: Neuroethical Considerationsmentioning

confidence: 99%

Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

Gazerani

2023

IJMS

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Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways to treat disease. Organoids of the liver, kidney, intestine, lung, and brain have been developed in recent years. Human brain organoids are used for understanding pathogenesis and investigating therapeutic options for neurodevelopmental, neuropsychiatric, neurodegenerative, and neurological disorders. Theoretically, several brain disorders can be modeled with the aid of human brain organoids, and hence the potential exists for understanding migraine pathogenesis and its treatment with the aid of brain organoids. Migraine is considered a brain disorder with neurological and non-neurological abnormalities and symptoms. Both genetic and environmental factors play essential roles in migraine pathogenesis and its clinical manifestations. Several types of migraines are classified, for example, migraines with and without aura, and human brain organoids can be developed from patients with these types of migraines to study genetic factors (e.g., channelopathy in calcium channels) and environmental stressors (e.g., chemical and mechanical). In these models, drug candidates for therapeutic purposes can also be tested. Here, the potential and limitations of human brain organoids for studying migraine pathogenesis and its treatment are communicated to generate motivation and stimulate curiosity for further research. This must, however, be considered alongside the complexity of the concept of brain organoids and the neuroethical aspects of the topic. Interested researchers are invited to join the network for protocol development and testing the hypothesis presented here.

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Organoids: a systematic review of ethical issues

Cited by 76 publications

References 122 publications

3D multicellular systems in disease modelling: From organoids to organ-on-chip

3D multicellular systems in disease modelling: From organoids to organ-on-chip

Research Trends in Lung Organoids: Bibliometric Analysis and Visualization

Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

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