302 results on '"Organoids"'
Search Results
2. Ethical-legal aspects of organoids and their use in research. Manage risks and legal constraints for the development of ethical research
- Author
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Sara Landini, Lucilla Gatt, Albina Candian, Simona Viciani, Emilia Giusti, Caterina Mugelli, Valentina Lunesu, Federica Gattillo, and Elisabetta Cerbai
- Subjects
organoids ,developmental biology ,regenerative medicine ,disease modelling ,Civil law ,K623-968 - Abstract
Organoids, briefly and simply stated, are miniature replicas of human organs and tissues: they derive from induced pluripotent stem cells (iPSC) or from adult cells and tissues, including tumors. They represent an important tool for personalized medicine and drug testing in general. At the moment the legal framework is incomplete and the focus is rather on ethical issues and the protection of privacy. The essay focuses on the legal framework looking for qualifying answers that can combine research development and protection of the person. Gli organoidi, detto in sintesi e semplicità, sono repliche in miniatura di organi e tessuti umani: derivano da cellule staminali pluripotenti indotte (iPSC) o da cellule e tessuti adulti, anche di tipo tumorale. Rappresentano un importante strumento per la medicina personalizzata e per la sperimentazione dei farmaci in generale. Al momento il quadro giuridico è lacunoso e l’attenzione è piuttosto sui temi etici e tutela della privacy. Il saggio si concentra sul framework giuridico cercando risposte qualificatorie che possano coniugare sviluppo della ricerca e tutela la persona.
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- 2023
- Full Text
- View/download PDF
3. Organoïdes hépatiques : définition, applications et perspectives.
- Author
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Wandji, Line Carolle Ntandja, Dubuquoy, Laurent, and Louvet, Alexandre
- Subjects
- *
PLURIPOTENT stem cells , *CELL communication , *DRUG development , *REGENERATIVE medicine , *INDIVIDUALIZED medicine - Abstract
Conventional two-dimensional (2D) culture systems have several limitations regarding the understanding of the pathophysiology of the liver (different phenotype from the one found in vivo, no consideration of the cellular microenvironment, etc.). Three-dimensional (3D) culture systems have therefore been developed in recent years, including spheroids and especially liver organoids, which now represent a promising alternative. Liver organoids are 3D structures derived from pluripotent stem cells, progenitors or differentiated cells capable of self-organizing via cell-cell or cell-matrix interactions in order to acquire the functional and architectural characteristics of the native tissue. Thus, they allow a better understanding of the pathophysiology of liver diseases and they offer new perspectives in personalized medicine. In pharmacology, the use of organoids would make it possible to overcome the various limitations of animal models and accelerate the development of new drugs. Moreover, in the persistent context of graft shortage worldwide, organoids bring a very interesting perspective in the field of regenerative medicine. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
- View/download PDF
4. Biomaterials for Artificial Organs and Organoids- A Comprehensive review
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Praveena K, Manjunatha, Awasthi Ankita, Dutt Amit, Khan Irfan, Maan Preeti, and Hussien Raghad Ahmed
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biomaterials ,artificial organs ,organoids ,regenerative medicine ,3d bioprinting ,bio fabrication ,Environmental sciences ,GE1-350 - Abstract
The technological development of biomaterials used in forming artificial organs and organoids indicates a revolutionary area within biomedical engineering and the field of regenerative medicine. This study provides an in-depth review of recent progress in biomaterials, emphasizing their design and use for fabricating artificial organs and organoids. The analysis proceeds with examining the necessary parameters for biomaterials in simulating the biological and biomechanical qualities of local tissues. The next effort turns towards synthesizing and characterizing innovative biomaterials, including biocompatible polymers, hydrogels, and bioactive scaffolds that can be tailored to suit specific organ systems. The paper provides an in-depth take on the developments in 3D biological printing and microfabrication techniques, emphasizing how they facilitate the synthesis of complicated, multicellular structures. The research also examines the integration of biomaterials when combined with stem cell technologies, focusing on their role in forming organs and the prospects for customized medical treatments. This review highlights the significant developments achieved in this area and the potential of these technologies in addressing the limited supply of organs, performing drug testing, and improving knowledge of the growth of organs and diseases.
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- 2024
- Full Text
- View/download PDF
5. [The contribution of cerebral organoids to the understanding and treatment of rare genetic diseases with neurodevelopmental disorders].
- Author
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El It F, Faivre L, Thauvin-Robinet C, Vitobello A, and Duplomb L
- Subjects
- Humans, Animals, Induced Pluripotent Stem Cells transplantation, Brain pathology, Genetic Diseases, Inborn therapy, Genetic Diseases, Inborn genetics, Genetic Diseases, Inborn pathology, Cell Differentiation genetics, Organoids, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders therapy, Neurodevelopmental Disorders pathology, Rare Diseases genetics, Rare Diseases therapy
- Abstract
Rare genetic diseases with neurodevelopmental disorders (NDDs) encompass several heterogeneous conditions (autism spectrum disorder (ASD), intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), specific learning disorder (SLD), among others). Currently, few treatments are available for these patients. The difficulty in accessing human brain samples and the discrepancies between human and animal models highlight the need for new research approaches. One promising approach is the use of the cerebral organoids. These 3D, self-organized structures, generated from induced pluripotent stem cells (iPSCs), enable the reproduction of the stages of human brain development, from the proliferation of neural stem cells to their differentiation into neurons, oligodentrocytes, and astrocytes. Cerebral organoids hold great promise in understanding brain development and in the search for treatments., (© 2024 médecine/sciences – Inserm.)
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- 2024
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6. Les sphéroïdes et les organoïdes d'oviducte: de nouveaux modèles pour mieux comprendre la fertilité.
- Author
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Reynaud, Karine, Mahé, Coline, Schmaltz, Lorraine, Mermillod, Pascal, and Saint-Dizier, Marie
- Subjects
- *
EMBRYOLOGY , *OVIDUCT , *GAMETES , *OVARIES , *UTERUS - Abstract
Spheroids and organoids are cellular models capable of selforganisation in 3 dimensions in vitro and which mimic the organisation of an organ. The oviduct, located between the ovary and the uterus, is the site of final gamete maturation, fertilisation and early embryonic development. Our objective is to develop oviduct spheroids and organoids to better understand the roles of this organ in the mechanisms of sperm storage and selection by the maternal organism, as well as in the embryo-maternal dialogue during the development of the young embryo. [ABSTRACT FROM AUTHOR]
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- 2022
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- View/download PDF
7. NOUVELLES STRATÉGIES D'ÉVALUATION DE LA TOXICITÉ EN TOXICOLOGIE.
- Author
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TETE, Arnaud, BORTOLI, Sylvie, and COUMOUL, Xavier
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- 2023
- Full Text
- View/download PDF
8. [Organoids in cancer research].
- Author
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Fessart D and Delom F
- Subjects
- Humans, Research, Organoids, Neoplasms therapy
- Published
- 2024
- Full Text
- View/download PDF
9. Les organoïdes en oncologie digestive : état des lieux et perspectives.
- Author
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Boilève, Alice, Cartry, Jérôme, Gelli, Maximiliano, Annereau, Maxime, Boige, Valérie, Ducreux, Michel, Jaulin, Fanny, and Malka, David
- Abstract
Les cancers digestifs représentent une cause majeure de mortalité. À ce jour, la chimiothérapie cytotoxique reste le traitement de référence de ces cancers puisque les deux avancées majeures récentes en cancérologie (médecine de précision et immunothérapie) n'ont amélioré qu'à la marge leur pronostic global. De plus, aucun standard thérapeutique n'est validé au-delà de la deuxième ou troisième ligne pour la plupart des cancers digestifs non colorectaux. Par conséquent, il est urgent de développer des approches alternatives de médecine personnalisée pour les cancers digestifs avancés. Les organoïdes sont un modèle prometteur de développement de médecine personnalisée. Les organoïdes sont des structures tridimensionnelles multicellulaires, cultivables ex vivo , qui conservent les caractéristiques génotypiques et phénotypiques de leur tissu ou de leur tumeur d'origine. Les organoïdes, avatars ex vivo des tissus normaux et pathologiques désormais reconnus, ouvrent des perspectives importantes pour la recherche biomédicale et clinique. Nous présentons ici les organoïdes dérivés de tissus et tumeurs digestives, qui peuvent être des modèles de compréhension des tumeurs digestives, puis nous discutons l'utilisation des organoïdes en recherche fondamentale et en médecine translationnelle et/ou de précision. Digestive cancers are a major cause of mortality worldwide. The two major recent breakthroughs in oncology – targeted therapies and immunotherapies – having only led to marginal therapeutic advances in digestive oncology, cytotoxic chemotherapy remains the mainstay of treatment of these cancers. Moreover, there is no standard treatment beyond the second or third line for most of digestive, non-colorectal cancers. Thus, there is an urgent unmet need to develop personalized medicine approaches for patients with advanced digestive cancers. Organoids are a promising tool for personalized medicine strategies. Grown from stem cells, organoids are tridimensional multicellular structures, cultivable ex vivo , that retain genotypic and phenotypic characteristics of their primary tissue or tumor of origin. Carcinoma-derived organoids are generated from biopsies or surgically resected tumors. These structures are now recognized as ex vivo avatars of physiological and pathological tissues, and open important perspectives for biomedical and clinical research. We present here an overview of digestive tissue- and tumor-derived organoids, as a model for the comprehension of digestive tumors and basic research. Then, we discuss the applicability of organoids in the clinic in innovative precision medicine strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
10. [For a good understanding and use of the term "organoids"].
- Author
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Chneiweiss H, Dubart-Kupperschmitt A, Duclos-Vallée JC, Clément B, Flacher V, Galzi JL, Gidrol X, Goureau O, Guasch G, Haiech J, Lemaitre C, Mahé MM, Martin S, Poulain L, Sebastiani C, Vergnolle N, and Yates F
- Subjects
- Humans, Organoids
- Published
- 2023
- Full Text
- View/download PDF
11. Les tumoroïdes, modèles précliniques en plein essor pour l’oncologie
- Author
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Lucie, Thorel, Romane, Florent, Marion, Perréard, Audrey, Vincent, Laurent, Poulain, Louis-Bastien, Weiswald, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Organoids ,Carcinogenesis ,Neoplasms ,[SDV]Life Sciences [q-bio] ,Humans ,Precision Medicine ,Medical Oncology - Abstract
The recent emergence of tumor organoid cultures, or tumoroids, has enriched the repertoire of preclinical models in oncology. These microtumors are obtained in vitro by including cells from patient tumor samples in an extracellular matrix and cultured in specific media. Very close to the tumor of origin, tumoroids can be amplified fairly rapidly from a small quantity of tissue, established with high success rate for most tumor types, easily genetically engineered, and stored in biobanks. Tumoroids thus offer numerous possibilities in terms of basic research, such as the study of carcinogenesis or mechanisms of chemoresistance, but also the identification of new targets and preclinical validation of new anti-cancer compounds or personalized medicine. Technological developments and enrichment of tumoroids with other cell types are currently ongoing to optimally exploit the full potential of these models.Les tumoroïdes, modèles précliniques en plein essor pour l’oncologie.La récente émergence des cultures d’organoïdes tumoraux, ou tumoroïdes, a permis d’enrichir le répertoire des modèles précliniques en oncologie. Très proches de la tumeur dont elles dérivent, ces microtumeurs offrent de nombreuses possibilités en termes de recherche fondamentale, telles que l’étude de la carcinogenèse ou de la chimioré-sistance, de validation préclinique de nouvelles molécules à visée anticancéreuse, ou encore de personnalisation des traitements. Divers développements techniques et l’enrichissement des tumoroïdes par l’addition d’autres types cellulaires sont actuellement en cours pour améliorer la pertinence de ces modèles et exploiter de façon optimale leur remarquable potentiel.
- Published
- 2022
12. [Patient-derived tumor organoids (or tumoroid) as valuable precision medicine tools]
- Author
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Marion, Perréard, Romane, Florent, Lucie, Thorel, Audrey, Vincent, Louis-Bastien, Weiswald, and Laurent, Poulain
- Subjects
Organoids ,Neoplasms ,Tumor Microenvironment ,Humans ,Precision Medicine ,Medical Oncology - Abstract
Review of literature shows that it is possible to establish tumor-derived organoids, or tumoroids, from almost any type of tumor, and that these "micro-tumors" could be used to develop functional assays allowing the prediction of the patient response to treatments and/or the identification of predictive molecular signatures associated with the development of these therapies. Although it is still essential to optimize culture conditions to promote and accelerate the establishment of tumoroids, or to recapitulate tumor microenvironment, many applications are now possible in the field of prediction of response to treatments and in guiding therapeutic decision-making. Using tumoroids as standard tools in clinical oncology could make precision oncology enter a new era in the coming decade. Numerous ongoing research and clinical trials conducted throughout the world aim to validate the interest of this approach.Les organoïdes dérivés de tumeurs (ou tumoroïdes), des outils de choix pour la médecine de précision en oncologie.Il est désormais possible d’établir des tumoroïdes à partir de presque tout type de tumeur, notamment en vue de la mise en place de tests fonctionnels prédictifs et/ou de l’identification de signatures moléculaires prédictives. Bien que l’optimisation des conditions de culture ou la complexification du micro-environnement des tumoroïdes soit encore nécessaire, de nombreuses applications sont déjà envisageables dans le domaine de la prédiction de la réponse aux traitements et de l’orientation de la décision thérapeutique. Par l’introduction de leur utilisation en clinique, l’oncologie de précision pourrait bien entrer dans une nouvelle ère dans le courant de la décennie à venir.
- Published
- 2022
13. [Are mini-brains watching you?]
- Author
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Gaël, Orieux and Olivier, Goureau
- Subjects
Neurons ,Organoids ,Induced Pluripotent Stem Cells ,Brain ,Humans ,Cell Differentiation ,Electrophysiological Phenomena - Abstract
iPSC-derived brain and retinal organoids represent biologically relevant 3D models. A new step in the field of brain and retinal organoids was reached a few months ago with the simultaneous development of brain and eye structures from human iPS cells within the same organoid. Single-cell mRNA sequencing analyses allowed the identification of various ocular and cerebral neuronal populations and electrophysiological recordings confirm the presence of functional and electrically active neurons. The coexistence within the same organoid of different cell types from visual and brain regions and the establishment of connections between these regions raise the intriguing question of its real or potential functionality and its ability to process higher-level visual information. This unique model could also be used to further understand the development of the human visual system and associated developmental diseases.Les mini-cerveaux vous observent-ils ?Les organoïdes cérébraux, comme les organoïdes rétiniens dérivés de cellules souches de type iPS, sont des modèles en trois dimensions (3D) biologiquement pertinents. Une étude récente du laboratoire de Jay Gopalakrishnan (université de Düsseldorf), en collaboration avec un groupe de l’université de Bonn et notre équipe de l’Institut de la vision à Paris, a montré la capacité des cellules iPS humaines à développer spontanément des organoïdes cérébraux incluant des structures oculaires rudimentaires bilatérales et symétriques. Cette innovation aboutissant à la formation d’organoïdes toujours plus complexes et proches des organes modélisés constitue une étape majeure pour comprendre comment l’œil humain se développe de concert avec le cerveau pour créer un système visuel fonctionnel.
- Published
- 2022
14. [Generating pancreatic islets organoids: Langerhanoids]
- Author
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Anastasia, Papoz, Flora, Clément, Camille, Laporte, Emily, Tubbs, Xavier, Gidrol, and Amandine, Pitaval
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Organoids ,Islets of Langerhans ,Insulin-Secreting Cells ,Islets of Langerhans Transplantation ,Humans ,Insulin - Abstract
The extension of islet transplantation to a wider number of Type 1 diabetic patients is compromised by the scarcity of donors, the reduced ex vivo survival of pancreatic islets and the use of immunosuppressive treatments. Islets of Langerhans isolated from brain-dead donors are currently the only cell source for transplantation. Thus, it is crucial to find an alternative and an abundant source of functional insulin secreting cells not only for clinical use but also for the development of research dedicated to the screening of drugs and to the development of new therapeutic targets. Several groups around the world, including ours, develop 3D culture models as Langerhanoids that closely mimick human pancreatic islets physiology. In this review, we describe recent advances to mimic the pancreatic niche (extracellular matrix, vascularization, microfluidics) allowing better functionality of Langerhanoids.Les Langerhanoïdes, des organoïdes d’îlots pancréatiques.Les îlots de Langerhans isolés de donneurs en état de mort encéphalique constituent actuellement la seule source de cellules pour la transplantation de patients atteints de diabète de type 1. Cette approche thérapeutique reste cependant compromise par la rareté des donneurs et par certains aspects techniques. L’utilisation de sources alternatives de cellules productrices d’insuline est donc un enjeu tant thérapeutique que pour la recherche pharmacologique. Plusieurs équipes dans le monde, dont la nôtre, développent des modèles de culture cellulaire en 3D, les Langerhanoïdes, qui sont physiologiquement proches des îlots pancréatiques humains. Dans cette revue, nous décrivons les récentes avancées mimant la niche pancréatique (matrice extracellulaire, vascularisation, microfluidique), permettant ainsi d’accroître la fonctionnalité de ces Langerhanoïdes.
- Published
- 2022
15. Les organoïdes normaux et leurs applications dans la recherche sur le cancer
- Author
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Frederic, Delom, Valérie, Le Morvan, Jacques, Robert, Delphine, Fessart, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Fondation ARC pour la Recherche sur Le Cancer
- Subjects
Biomedical Research ,Lung Neoplasms ,Carcinogenesis ,Modeling ,Bronchi ,Cell Differentiation ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Organoids ,Modélisation ,Neoplasms ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Tumor Cells, Cultured ,Genetics ,Humans ,Cell Culture Techniques, Three Dimensional ,Organoïdes ,Cell Self Renewal ,Precision Medicine ,Génétique ,Cancer - Abstract
National audience; Three-dimensional (3D) culture of organoids from primary cells (wild type) or tumoroids from tumor cells, is used to study the physiological mechanisms in vivo, in order to model normal or tumor tissues more accurately than conventional two-dimensional (2D) culture. The features of this 3D culture, such as the three-dimensional structure, the self-renewal capacity and differentiation are preserved and appropriate to cancer study since their cellular characteristics are very similar to in vivo models. Here, we summarize the recent advances in the rapidly evolving field of organoids and their applications to cancer biology, clinical research and personalized medicine.
- Published
- 2022
16. Etude du rôle des Lymphocytes Intraépithéliaux innés dans la réponse immune protectrice contre Cryptosporidium parvum
- Author
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Hariss, Fatima, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Université Libanaise, Bertrand Meresse, Mohamad Ezzedine, and STAR, ABES
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Organoïds ,Innate IELs ,Cryptosporidium ,Organoïdes ,LIE innés ,Crytosporidium parvum ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Intraepithelial lymphocytes (IEL) reside between intestinal epithelial cells and thus are the first immune cells to contact intestinal pathogens. In addition to respond rapidly to infection, they regulate intestinal homeostasis and maintain the epithelial barrier. This wide range of functions is achieved by distinct subsets of T and innate lymphocytes. Innate IEL which share many features with NK/ILC1 cells have been identified recently. These cells dominate the gut epithelium at birth and when the adaptive immunity is compromised. Their role in the immune response against intestinal pathogens remains however poorly studied.During my PhD thesis, I have investigated the role of innate IEL subsets in Crysptosporidium infection. Crysptosporidium is a common parasite that infects the gut epithelium. The infection is self-limiting in immunocompetent individuals, but it can be severe in immunocompromised individuals and children in whom innate IEL dominate.To study the specific role of innate IEL, we have developed an in vitro model that consist to co-culture mice 3D intestinal organoids infected with C parvum with innate IELs from RAG2-/- mice. Thanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IEL secrete IFN-ƴ in response to C parvum infection, the IFN-ƴ secretion was not sufficient to inhibit parasite proliferation. The protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis revealed that infected epithelial cells down regulated serpinb9b, a granzyme inhibitor, and thus may be more sensitive to cytotoxic attack., Les lymphocytes intraépithéliaux (LIE) résident entre les cellules épithéliales (CE) intestinales et sont donc les premières cellules immunitaires à entrer en contact avec les agents pathogènes. En plus de répondre rapidement à l'infection, ils régulent l'homéostasie intestinale et maintiennent la barrière épithéliale. Ces fonctions sont assurées par différentes sous-populations de lymphocytes T et innés. Les LIE innés ont été identifiés récemment. Ils sont majoritaires dans l'épithélium intestinal à la naissance et lorsque l'immunité adaptative est compromise. Leur rôle dans la réponse immunitaire contre les pathogènes intestinaux reste cependant peu étudié.Au cours de ma thèse, j'ai étudié le rôle des LIE innés dans l'infection à Cryptosporidium, un parasite opportuniste qui infecte l'épithélium intestinal. L'infection est bénigne chez les individus immunocompétents, mais peut être sévère chez les individus immunodéprimés et les enfants.Pour étudier le rôle spécifique des LIE innés, nous avons développé un modèle in vitro qui consiste à co-cultiver des organoïdes intestinaux murins infectés par C parvum avec des LIE innés de souris RAG2-/-. Grâce à ce modèle original, nous avons démontré que les LIE innés contrôlent la prolifération du parasite et bien qu’ils sécrètent l'IFN-ƴ en réponse à C parvum, cette sécrétion n’est pas suffisante pour inhiber la prolifération du parasite. L'effet protecteur des LIE innés est en fait médié par un mécanisme cytotoxique dépendant des granzymes. L’analyse du transcriptome a révélé que les CE infectées régulent négativement la serpinb9b, un inhibiteur de granzyme, et pourraient ainsi être plus sensibles aux attaques cytotoxiques.
- Published
- 2021
17. Study of the role of innate intraepithelial lymphocytes in the protective immune response against Cryptosporidium parvum
- Author
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Hariss, Fatima, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Université Libanaise, Bertrand Meresse, Mohamad Ezzedine, and STAR, ABES
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Organoïds ,Innate IELs ,Cryptosporidium ,Organoïdes ,LIE innés ,Crytosporidium parvum ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Intraepithelial lymphocytes (IEL) reside between intestinal epithelial cells and thus are the first immune cells to contact intestinal pathogens. In addition to respond rapidly to infection, they regulate intestinal homeostasis and maintain the epithelial barrier. This wide range of functions is achieved by distinct subsets of T and innate lymphocytes. Innate IEL which share many features with NK/ILC1 cells have been identified recently. These cells dominate the gut epithelium at birth and when the adaptive immunity is compromised. Their role in the immune response against intestinal pathogens remains however poorly studied.During my PhD thesis, I have investigated the role of innate IEL subsets in Crysptosporidium infection. Crysptosporidium is a common parasite that infects the gut epithelium. The infection is self-limiting in immunocompetent individuals, but it can be severe in immunocompromised individuals and children in whom innate IEL dominate.To study the specific role of innate IEL, we have developed an in vitro model that consist to co-culture mice 3D intestinal organoids infected with C parvum with innate IELs from RAG2-/- mice. Thanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IEL secrete IFN-ƴ in response to C parvum infection, the IFN-ƴ secretion was not sufficient to inhibit parasite proliferation. The protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis revealed that infected epithelial cells down regulated serpinb9b, a granzyme inhibitor, and thus may be more sensitive to cytotoxic attack., Les lymphocytes intraépithéliaux (LIE) résident entre les cellules épithéliales (CE) intestinales et sont donc les premières cellules immunitaires à entrer en contact avec les agents pathogènes. En plus de répondre rapidement à l'infection, ils régulent l'homéostasie intestinale et maintiennent la barrière épithéliale. Ces fonctions sont assurées par différentes sous-populations de lymphocytes T et innés. Les LIE innés ont été identifiés récemment. Ils sont majoritaires dans l'épithélium intestinal à la naissance et lorsque l'immunité adaptative est compromise. Leur rôle dans la réponse immunitaire contre les pathogènes intestinaux reste cependant peu étudié.Au cours de ma thèse, j'ai étudié le rôle des LIE innés dans l'infection à Cryptosporidium, un parasite opportuniste qui infecte l'épithélium intestinal. L'infection est bénigne chez les individus immunocompétents, mais peut être sévère chez les individus immunodéprimés et les enfants.Pour étudier le rôle spécifique des LIE innés, nous avons développé un modèle in vitro qui consiste à co-cultiver des organoïdes intestinaux murins infectés par C parvum avec des LIE innés de souris RAG2-/-. Grâce à ce modèle original, nous avons démontré que les LIE innés contrôlent la prolifération du parasite et bien qu’ils sécrètent l'IFN-ƴ en réponse à C parvum, cette sécrétion n’est pas suffisante pour inhiber la prolifération du parasite. L'effet protecteur des LIE innés est en fait médié par un mécanisme cytotoxique dépendant des granzymes. L’analyse du transcriptome a révélé que les CE infectées régulent négativement la serpinb9b, un inhibiteur de granzyme, et pourraient ainsi être plus sensibles aux attaques cytotoxiques.
- Published
- 2021
18. [Hepatic organoids: What are the challenges?]
- Author
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Eléanor, Luce, Antonietta, Messina, Amandine, Caillaud, Karim, Si-Tayeb, Bertrand, Cariou, Etienne, Bur, Anne, Dubart-Kupperschmitt, and Jean-Charles, Duclos-Vallée
- Subjects
Organoids ,Pluripotent Stem Cells ,Liver ,Induced Pluripotent Stem Cells ,Hepatocytes ,Humans ,Cell Differentiation - Abstract
The study and understanding of liver organogenesis have allowed the development of protocols for pluripotent stem cells differentiation to overcome the lack of primary cells, providing an almost unlimited source of liver cells. However, as their differentiation in conventional 2D culture systems has shown serious limits, hepatic organoids derived from human pluripotent stem cells represent a promising alternative. These complex and organized structures, containing one or more cell types, make it possible to recapitulate in vitro some of the organ functions, thus enabling numerous applications such as the study of the liver development, the mass production of functional liver cells for transplantation or the development of bioartificial livers, as well as the in vitro modeling of hepatic pathologies allowing high throughput applications in drug screening or toxicity studies. Economic and ethical issues must also be taken into account before using these organoids in therapeutic applications.Les organoïdes hépatiques - Quels sont les enjeux ?L’étude et la compréhension de l’organogenèse du foie ont permis le développement de protocoles de différenciation des cellules souches pluripotentes afin de pallier le manque de cellules primaires, offrant ainsi une source quasi illimitée de cellules hépatiques. La différenciation de ces cellules dans des systèmes de culture conventionnels en deux dimensions (2D) ayant cependant montré ses limites, des organoïdes hépatiques ont été dérivés de cellules souches pluripotentes humaines et représentent désormais une alternative prometteuse. Ces structures 3D, complexes et organisées, intégrant un ou plusieurs types cellulaires, permettent de reproduire in vitro une ou plusieurs fonctions de l’organe, et ouvrent ainsi la voie à de nombreuses applications, comme l’étude du développement du foie, la production en masse de cellules hépatiques fonctionnelles pour la transplantation ou le développement de foies bioartificiels, sans oublier la modélisation de pathologies hépatiques permettant le criblage à haut débit de médicaments ou des études de toxicité. Des enjeux économiques et éthiques doivent également être pris en considération avant une utilisation de ces organoïdes pour des applications thérapeutiques.
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- 2021
19. 3D Tumor organoid models produced by cellular capsules technology CCT
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Gaëlle, Recher, Amaël, Mombereau, Adeline, Boyreau, Pierre, Nassoy, and Laëtitia, Andrique
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Epithelial-Mesenchymal Transition ,Alginates ,Cell Communication ,Cell Encapsulation ,Coculture Techniques ,Extracellular Matrix ,Organoids ,Cancer-Associated Fibroblasts ,Spheroids, Cellular ,Tumor Cells, Cultured ,Tumor Microenvironment ,Humans ,Cell Culture Techniques, Three Dimensional ,Neoplasm Invasiveness ,Cell Proliferation - Abstract
Monolayer cultures of cell lines and derived-patient cells have long been the in vitro model of choice in oncology. In particular, these models have made it possible to decipher the mechanisms that determine tumor proliferation and invasion. However these 2D models are insufficient because they do not take into account the spatial organization of cells and their interactions with each other or with the extracellular matrix. In the context of cancer, there is a need to develop new 3D (tumoroid) models in order to gain a better understanding of the development of these pathologies but also to assess the penetration of drugs through a tissue and the associated cellular response. We present here the cell capsule technology (CCT), which allows the production of different tumoroid models: simple or more complex 3D culture models including co-culture of tumor cells with components of the microenvironment (fibroblasts, matrix, etc.). The development of these new 3D culture systems now makes it possible to propose refined physiopathological models that will allow the implementation of improved targeted therapeutic strategies.
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- 2021
20. [Spheroids to organoids: Solid cancer models for anticancer drug discovery]
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George, Alzeeb, Laurent, Corcos, and Catherine, Le Jossic-Corcos
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Organoids ,Neoplasms ,Spheroids, Cellular ,Drug Discovery ,Tumor Cells, Cultured ,Tumor Microenvironment ,Humans ,Antineoplastic Agents ,Cell Culture Techniques, Three Dimensional ,Drug Screening Assays, Antitumor ,Precision Medicine ,Models, Biological - Abstract
Cell culture is an important and necessary technology in oncology research. Currently, two-dimensional (2D) cell culture models are the most widely used, but they cannot reproduce the complexity and pathophysiology of tumors in vivo. This may be a major cause of the high rate of attrition of anticancer drugs entering clinical trials, the rate of new anticancer drugs entering the market being less than 5 %. One way to improve the success of new cancer drugs in the clinic is based on the use of three-dimensional (3D) cell culture models, more able to represent the complex environment and architecture of tumors. These 3D culture systems are also a powerful research tool for modeling the evolution of cancer from early stages to metastasis. Spheroids and organoids, the most adaptable models among 3D culture systems, are beginning to be used in pharmaceutical research and personalized medicine. In this article, we review the use of spheroids and organoids by highlighting their differences, discussing their impact on drug development, and looking at future challenges.
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- 2021
21. Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland
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Charlotte Nys, Patrick Matthys, Adrian Janiszewski, Emma Laporte, Diether Lambrechts, Elodie Modave, Marie-Isabelle Garcia, Hiroto Kobayashi, Benoit Cox, Joel Chappell, Vincent Pasque, Florient Hermans, Hugo Vankelecom, Bert Malengier-Devlies, and Annelies Vennekens
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Aging ,pituitary ,Transcriptome ,Mice ,stem cells ,Organoid ,Endocrine system ,Animals ,Interleukin 6 ,organoids ,Cell Proliferation ,Inflammation ,Multidisciplinary ,biology ,Activator (genetics) ,Interleukin-6 ,Stem Cells ,interleukin-6 ,aging ,Biologie moléculaire ,Biological Sciences ,In vitro ,Cell biology ,Up-Regulation ,Organoids ,Phenotype ,Pituitary Gland ,biology.protein ,Biologie cellulaire ,Stem cell ,Signal transduction ,Single-Cell Analysis - Abstract
Stem cells in the adult pituitary are quiescent yet show acute activation upon tissue injury. The molecular mechanisms underlying this reaction are completely unknown. We applied single-cell transcriptomics to start unraveling the acute pituitary stem cell activation process as occurring upon targeted endocrine cell-ablation damage. This stem cell reaction was contrasted with the aging (middle-aged) pituitary, known to have lost damage-repair capacity. Stem cells in the aging pituitary show regressed proliferative activation upon injury and diminished in vitro organoid formation. Single-cell RNA sequencing uncovered interleukin-6 (IL-6) as being up-regulated upon damage, however only in young but not aging pituitary. Administering IL-6 to young mice promptly triggered pituitary stem cell proliferation, while blocking IL-6 or associated signaling pathways inhibited such reaction to damage. By contrast, IL-6 did not generate a pituitary stem cell activation response in aging mice, coinciding with elevated basal IL-6 levels and raised inflammatory state in the aging gland (inflammaging). Intriguingly, in vitro stem cell activation by IL-6 was discerned in organoid culture not only from young but also from aging pituitary, indicating that the aging gland's stem cells retain intrinsic activatability in vivo, likely impeded by the prevailing inflammatory tissue milieu. Importantly, IL-6 supplementation strongly enhanced the growth capability of pituitary stem cell organoids, thereby expanding their potential as an experimental model. Our study identifies IL-6 as a pituitary stem cell activator upon local damage, a competence quenched at aging, concomitant with raised IL-6/inflammatory levels in the older gland. These insights may open the way to interfering with pituitary aging. ispartof: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA vol:118 issue:25 ispartof: location:United States status: published
- Published
- 2021
22. [Alternative methods to animal testing, present and future].
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Marano F
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- Animals, Animal Testing Alternatives methods, Animal Experimentation, Biomedical Research
- Abstract
Alternative methods to animal testing are used in fundamental and clinical research, for the realization of studies for regulatory purposes, and also screening operations in the development of new molecules. They are based on in vitro (cell models) or in silico (mathematical models) replacement methods. They have been largely promoted by the 3Rs rule (Replace, Reduce, Refine) which aims at regulating animal experimentation. For biomedical research, these different methods are valuable tools for better understanding the physiology of organisms and the mechanisms of the effects of chemicals and physical agents on them., (© Société de Biologie, 2023.)
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- 2023
- Full Text
- View/download PDF
23. [Patient-derived tumor organoids (or tumoroid) as valuable precision medicine tools].
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Perréard M, Florent R, Thorel L, Vincent A, Weiswald LB, and Poulain L
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- Humans, Organoids, Medical Oncology, Tumor Microenvironment, Precision Medicine, Neoplasms genetics, Neoplasms therapy
- Abstract
Review of literature shows that it is possible to establish tumor-derived organoids, or tumoroids, from almost any type of tumor, and that these "micro-tumors" could be used to develop functional assays allowing the prediction of the patient response to treatments and/or the identification of predictive molecular signatures associated with the development of these therapies. Although it is still essential to optimize culture conditions to promote and accelerate the establishment of tumoroids, or to recapitulate tumor microenvironment, many applications are now possible in the field of prediction of response to treatments and in guiding therapeutic decision-making. Using tumoroids as standard tools in clinical oncology could make precision oncology enter a new era in the coming decade. Numerous ongoing research and clinical trials conducted throughout the world aim to validate the interest of this approach., (© 2022 médecine/sciences – Inserm.)
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- 2022
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24. [Patient-derived tumor organoids (or tumoroid), a growing preclinical model for oncology].
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Thorel L, Florent R, Perréard M, Vincent A, Poulain L, and Weiswald LB
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- Humans, Medical Oncology, Precision Medicine, Carcinogenesis, Organoids, Neoplasms therapy
- Abstract
The recent emergence of tumor organoid cultures, or tumoroids, has enriched the repertoire of preclinical models in oncology. These microtumors are obtained in vitro by including cells from patient tumor samples in an extracellular matrix and cultured in specific media. Very close to the tumor of origin, tumoroids can be amplified fairly rapidly from a small quantity of tissue, established with high success rate for most tumor types, easily genetically engineered, and stored in biobanks. Tumoroids thus offer numerous possibilities in terms of basic research, such as the study of carcinogenesis or mechanisms of chemoresistance, but also the identification of new targets and preclinical validation of new anti-cancer compounds or personalized medicine. Technological developments and enrichment of tumoroids with other cell types are currently ongoing to optimally exploit the full potential of these models., (© 2022 médecine/sciences – Inserm.)
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- 2022
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- View/download PDF
25. Analyseur optofluidique pour capsules cellulaires
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Hélaine, Nelson, Laboratoire Photonique, Numérique et Nanosciences (LP2N), Université de Bordeaux (UB)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux, and Pierre Nassoy
- Subjects
Organoids ,[PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics] ,Light-Living matter interaction ,Interaction lumière-Tissu vivant ,Optofluidique ,Optofluidics ,Organoïdes - Abstract
This work consists in the design and use of a micro-device dedicated to the analysis of multicellular aggregates based on the measure of light attenuation. The celllular capsule technology, which was patented by the host team, can generate several thousand spheroids/organoids in a few seconds. Our objective is to characterize these submillimetric samples encapsulated in a transparent shell by measuring their radius and extinction coefficient without resorting to an inherently slow and low throughput imaging technique. To exploit the high throughput capabilities of the technique, we propose to develop a fluorescence-free optofluidic analyzer inspired from classical cytometers. We first simulated the interaction of a Gaussian laser beam with a sphere of known radius and extinction coefficient and developed the optical detection module. Experimental measurements were compared with simulations to validate our approach. Then, we designed a microfluidic device aimed at conveying the heavy cellular capsules through the beam using a 3D printing approach. Finally, our optical system was combined with the fluidic module and modified to determine the displacement speed of each conveyed capsule as it interacts with the laser beam. We provide a proof of concept that the high throughput of such an instrument allows the analysis of a very large number of samples (several thousands) in a short time (a few hours). The instrument was then used to determine the growth curves of two tumor lymphocyte cell lines ("liquid" tumors), as well as the modifications in the extinction coefficients when cancer cells are fixed and when adipose stem cells undergo differentiation into adipocytes that store lipid droplets. The sensitivity of our instrument is compatible with a further use in pre-clinical trials on tumour cell aggregates to estimate the efficacy of chemotherapy treatments for instance. Finally, an "open source" dimension was integrated into the design of the electronic and software parts of the project to promote copying and improvement, e.g through the addition of a sorting module.; Ce travail de thèse consiste en la conception et l’utilisation d’un système d’analyse d’agrégats multicellulaires par mesure de l’atténuation de la lumière. La technologie des capsules cellulaires brevetée au sein de l’équipe d’accueil peut générer plusieurs milliers de sphéroïdes/organoïdes en quelques secondes. L’objectif est ici de caractériser ces échantillons submillimétriques encapsulés dans une coque transparente par une mesure de leur rayon et de leur coefficient d’atténuation, sans recourir à une technique d’imagerie intrinsèquement lente et bas débit. Pour exploiter le fait que la technique de production est à haut débit, nous proposons de développer un analyseur optofluidique inspiré dans son principe de fonctionnement des cytomètres classiques, mais sans marquage fluorescent des échantillons. Nous avons tout d’abord simulé l’interaction d’un faisceau laser gaussien avec une sphère de rayon et coefficient d’atténuation connus, puis développé le module optique de détection. Les mesures expérimentales ont été confrontées aux simulations pour valider notre approche. Ensuite, nous avons conçu un circuit microfluidique capable de convoyer les capsules cellulaires pesantes au travers du faisceau en utilisant une approche par impression 3D. Enfin, notre système optique a été combiné au module fluidique et modifié pour déterminer la vitesse de déplacement de chaque capsule convoyée au moment de son interaction avec le faisceau d’interrogation. Nous apportons la preuve de concept que le caractère haut-débit d’un tel instrument permet d’analyser un très grand nombre d’échantillons (plusieurs milliers) en peu de temps (quelques heures). L’instrument présenté a été utilisé pour déterminer les courbes de croissance de deux lignées cellulaires de lymphocytes tumoraux (tumeurs « liquides »), ainsi que des modifications de coefficient d’atténuation liées à la fixation sur cellules hépatiques tumorales ou à la stimulation chimique de cellules souches adipeuses qui génèrent des chapelets de gouttelettes lipidiques au cours de leur différenciation. La sensibilité de notre instrument laisse envisager son utilisation dans le cadre d’essais précliniques sur des agrégats de cellules tumorales, afin de déterminer la croissance de ces « micro-tumeurs » et donc estimer l’efficacité de traitements de chimiothérapie par exemple. Enfin, un aspect « open source » a été souhaité dans la conception de l’infrastructure électronique et informatique du prototype, ouvrant ce travail à la copie et l’amélioration, notamment par l’ajout d’un module de tri d’échantillons.
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- 2020
26. [Photoreceptor cell transplantation for future treatment of retinitis pigmentosa]
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Olivier, Goureau and Gaël, Orieux
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Organoids ,Pluripotent Stem Cells ,Tissue Culture Techniques ,Therapies, Investigational ,Induced Pluripotent Stem Cells ,Retinal Degeneration ,Tissue and Organ Harvesting ,Animals ,Humans ,Photoreceptor Cells ,Severity of Illness Index ,Retina ,Retinitis Pigmentosa - Abstract
In inherited retinal diseases such retinitis pigmentosa, characterized by progressive loss of light sensitive neurons (photoreceptors), cell therapy is now considered as an attractive strategy. Photoreceptor cell replacement would be valuable for restoring function to retinas in a way that is independent from the cause of the disease. With advances in stem cell biology, considerable strides have been made towards the generation of retinal cells, in particular with the development of 3D culture systems allowing the generation of retinal organoids from pluripotent stem cells. In this review, we present a state-of-the art of preclinical strategies conducted in animal models for photoreceptor replacement from stem cell-derived photoreceptors and we discuss the important obstacles to overcome in the future.Nouvelle approche thérapeutique pour les rétinites pigmentaires - La transplantation de photorécepteurs dérivés de cellules souches.Dans les maladies dégénératives de la rétine affectant les photorécepteurs, la transplantation de cellules permettant la restauration de la vision est aujourd’hui envisagée. La dernière décennie a vu des progrès remarquables dans la génération de cellules de rétine à partir de cellules souches pluripotentes humaines avec, en particulier, le développement de systèmes de culture en trois dimensions (3D) permettant la génération d’organoïdes de rétine. Dans cette revue, nous faisons un état des lieux sur les stratégies précliniques menées dans des modèles animaux pour le remplacement des photorécepteurs par des photorécepteurs dérivés de cellules souches et présentons les obstacles importants qui restent à être surmontés.
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- 2020
27. [Retinal organoids as a new tool for understanding and treating retinal diseases]
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Olivier, Goureau, Sacha, Reichman, and Gaël, Orieux
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Organoids ,Tissue Culture Techniques ,Retinal Diseases ,Therapies, Investigational ,Animals ,Humans ,Models, Biological ,Cells, Cultured ,Retina - Abstract
Generation of retinal organoids from pluripotent stem cells represents an important advance in the study of retinal development and offer new perspectives for the study of retinal diseases missing suitable animal models. Understanding the key stages of retinal development in vertebrates enabled to design protocols to generate self-organized three-dimensional structures derived from pluripotent stem cells and containing all retinal cell types. In addition to their application in basic research, such as the characterization of molecular and cellular mechanisms in retinal pathophysiology, these miniature organs also open up encouraging prospects in the field of cell therapy or the screening of therapeutic molecules, although some obstacles remain to be overcome.Les organoïdes de rétine - Un nouvel outil pour comprendre et traiter les maladies rétiniennes.Les organoïdes de rétine dérivés de cellules souches pluripotentes représentent une avancée importante pour l’étude du développement de la rétine et offrent de nouvelles possibilités pour l’étude des maladies associées difficilement modélisables chez l’animal. La compréhension des étapes clefs du développement de la rétine chez les vertébrés a conduit à la mise au point de protocoles permettant d’obtenir, à partir de cellules souches pluripotentes, des structures tridimensionnelles auto-organisées contenant l’ensemble des types cellulaires de la rétine. Outre les applications en recherche fondamentale, ces organes miniatures ouvrent des perspectives encourageantes dans le domaine de la thérapie cellulaire ou le criblage de molécules thérapeutiques.
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- 2020
28. [News drugs and evolution towards personalized treatment for cystic fibrosis]
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H, Boboli, J, Pirson, M C, Seghaye, and C, Kempeneers
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Organoids ,Cystic Fibrosis ,Genotype ,Mutation ,Cystic Fibrosis Transmembrane Conductance Regulator ,Humans ,Precision Medicine - Abstract
Cystic fibrosis is a genetic disorder responsible for the production of a defective transmembrane protein. In recent years, new protein modulators have been developed. They aim to treat the underlying cause of the disease. The results on the biomarkers of the function of the CFTR protein and on the clinical outcomes are very encouraging. However, there is an individual heterogeneity in the response to modulators within a same genotype. Furthermore, clinical trials focus on the most common mutations in the CFTR gene, in particular DF508. Intestinal organoids, a new model of ex vivo study, could offer a quick approach to increase access to effective treatment for all patients with cystic fibrosis regardless of their CFTR genotype. Organoids could enable personalized treatment of cystic fibrosis.La mucoviscidose est une maladie génétique responsable de la production d’une protéine transmembranaire défectueuse. Au cours des dernières années, se sont développés des traitements modulateurs ciblant les défauts spécifiques de la protéine causés par les mutations du gène CFTR. Les résultats sur les biomarqueurs de la fonction de la protéine CFTR et sur les paramètres cliniques sont très encourageants. Cependant, une hétérogénéité individuelle dans la réponse aux modulateurs est observée. De plus, les essais cliniques se focalisent sur les mutations les plus fréquentes du gène, en particulier DF508. Les organoïdes intestinaux, un nouveau modèle d’étude ex vivo, pourraient offrir une approche rapide pour majorer l’accès à un traitement efficace à tous les patients, quel que soit leur génotype CFTR. Les tests in vitro sur les organoïdes rendent possible l’évolution vers une médecine personnalisée pour les patients atteints de mucoviscidose.
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- 2020
29. Les organoïdes pulmonaires
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Bourguignon, Chloé, Vernisse, Charlotte, Mianné, Joffrey, Fieldes, Mathieu, Ahmed, Engi, Petit, Aurélie, Vachier, Isabelle, Bertrand, Thierry Lavabre, Assou, Said, Bourdin, Arnaud, De Vos, John, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
- Subjects
Gene Editing ,Tissue Scaffolds ,Pulmonary Gas Exchange ,[SDV]Life Sciences [q-bio] ,Cell Culture Techniques ,Bioengineering ,Respiratory Mucosa ,Carbon Dioxide ,Models, Biological ,Organoids ,Oxygen ,Alveolar Epithelial Cells ,Animals ,Humans ,Lung ,Cells, Cultured - Abstract
As burden of chronic respiratory diseases is constantly increasing, improving in vitro lung models is essential in order to reproduce as closely as possible the complex pulmonary architecture, responsible for oxygen uptake and carbon dioxide clearance. The study of diseases that affect the respiratory system has benefited from in vitro reconstructions of the respiratory epithelium with inserts in air/liquid interface (2D) or in organoids able to mimic up to the arborescence of the respiratory tree (3D). Recent development in the fields of pluripotent stem cells-derived organoids and genome editing technologies has provided new insights to better understand pulmonary diseases and to find new therapeutic perspectives.Les organoïdes pulmonaires.L’impact en santé publique des pathologies respiratoires chroniques ne cesse de croître. Dans ce contexte, il paraît indispensable d’améliorer les modèles d’études du poumon afin de reproduire au plus proche l’architecture pulmonaire complexe, garante des fonctions d’oxygénation et d’épuration du gaz carbonique. Les connaissances actuelles en physiopathologie respiratoire résultent en partie des études de modèles de reconstitution d’épithélium bronchique in vitro à partir de cellules primaires, en deux dimensions sur des inserts, ou en trois dimensions, en organoïdes mimant jusqu’à l’arborescence pulmonaire. Le développement de ces modèles in vitro a connu un nouvel essor grâce aux organoïdes pulmonaires issus de cellules souches pluripotentes et la démocratisation des outils d’édition du génome. Ces apports technologiques récents offrent de nouvelles perspectives en matière de thérapeutiques ou de compréhension physiopathologique et pourraient, dans le futur, ouvrir les portes de la médecine régénératrice pulmonaire.
- Published
- 2020
30. [Organoids: new perspectives and ethical issues]
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Hervé, Chneiweiss
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Organoids ,Human Experimentation ,Tissue and Organ Procurement ,Induced Pluripotent Stem Cells ,Cell Culture Techniques ,Animals ,Humans ,Bioengineering ,Cells, Cultured - Published
- 2020
31. [Organoids from pancreatic ductal adenocarcinoma]
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Nelson, Dusetti and Juan, Iovanna
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Gene Expression Regulation, Neoplastic ,Organoids ,Pancreatic Neoplasms ,Gene Expression Profiling ,Primary Cell Culture ,Tumor Cells, Cultured ,Humans ,Cell Separation ,Adenocarcinoma ,Precision Medicine ,Transcriptome ,Carcinoma, Pancreatic Ductal ,Cell Proliferation - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a rapidly evolving and most frequently fatal disease. Despite the enormous progress in understanding the mechanisms related to PDAC pathogenesis, the impact on patient management has not yet been possible. Pancreatic organoids can be generated from small amounts of tissue. One of the most promising applications of organoids is that they can serve as a platform for selecting the right drugs for each patient. This approach has the potential to identify individual therapeutic vulnerabilities by allowing the personalization of treatments. However, these analyzes require several weeks before obtaining enough organoids from the same individual, to carry out the tests with several drugs, and to analyze the results, which limits its use in current clinical practice for the patients with a PDAC, whose it must be remembered that half die within 6 months of diagnosis. To overcome this obstacle, we assessed the ability of transcriptomic molecular signatures to identify patients with a particular sensitivity profile to a given treatment. The approaches based on transcriptomic profiling have the enormous advantage of using very little biological material and thus significantly reducing the time to arrive at the selection of more effective drugs to each patient.Organoïdes dérivés des adénocarcinomes pancréatiques.L’adénocarcinome canalaire pancréatique (PDAC) est une maladie à évolution rapide le plus souvent mortelle. Malgré les énormes progrès dans la compréhension des mécanismes reliés à la pathogenèse du PDAC, l’impact de ces avancées sur la prise en charge des patients se fait encore attendre. L’une des applications les plus prometteuses des organoïdes est qu’ils peuvent servir de plate-forme pour la sélection de drogues mieux adaptées à chaque patient. Les organoïdes pancréatiques peuvent être générés à partir de petites quantités de tissu. Cette approche a ainsi le potentiel d’identifier les vulnérabilités thérapeutiques individuelles en permettant de personnaliser les traitements. Ces analyses nécessitent néanmoins plusieurs semaines avant d’obtenir suffisamment d’organoïdes d’un même individu, de pouvoir réaliser les tests de plusieurs drogues et d’analyser les résultats, ce qui limite l’utilisation de cette méthodologie en pratique clinique courante pour les patients, dont il faut se rappeler que la moitié décède dans les 6 mois qui suivent le diagnostic. Pour surmonter cet obstacle, nous avons évalué la capacité d’identification de patients présentant un profil particulier de sensibilité à un traitement donné, de signatures moléculaires transcriptomiques. Les approches fondées sur ce type de profilage transcriptomique ont l’énorme avantage d’utiliser très peu de matériel biologique. Elles permettent également de réduire sensiblement le temps pour la sélection des drogues qui se révèlent plus efficaces pour un patient défini.
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- 2020
32. [From human pluripotent stem cells to custom-made intestinal organoids]
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Flatres, Charlotte, Loffet, Élise, Neunlist, Michel, Mahé, Maxime, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-17-CE14-0021,SyNEDI,Rôle du Système Nerveux Entérique sur le Développement Intestinal chez l'Homme.(2017)
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Pluripotent Stem Cells ,Gastrointestinal Diseases ,Induced Pluripotent Stem Cells ,Drug Evaluation, Preclinical ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Cell Differentiation ,Gastrointestinal Tract ,Intestines ,Organoids ,Tissue Culture Techniques ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Animals ,Humans ,Regeneration ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Cells, Cultured - Abstract
The study of gut diseases is often limited by the access to human biological tissues and animal models that do not faithfully mimic the human pathologies. In this context, the development of intestinal organoids from human pluripotent stem cells is paving the way of gastrointestinal physiology and digestive disease study. In this review, we recall the embryonic development of the digestive tract and its translation to human pluripotent stem cell differentiation. We also present the different types of intestinal organoids that can be generated, as well as their applications in research.Façonner l’intestin à partir des cellules souches pluripotentes humaines.L’étude des maladies digestives est parfois limitée par l’accès aux tissus de patients et les modèles précliniques ne sont pas toujours fidèles aux pathologies observées chez l’homme. Dans ce contexte, le développement d’organoïdes intestinaux à partir de cellules souches pluripotentes humaines représente une avancée importante dans l’étude des processus physiologiques et des pathologies digestives. Dans cette revue, nous rappelons les étapes majeures du développement du tractus digestif chez l’homme et décrivons le rationnel de la différenciation dirigée des cellules souches pluripotentes humaines. Nous faisons également un état des lieux sur les différents types d’organoïdes intestinaux existants et leurs applications en recherche fondamentale et préclinique. Enfin, nous discutons des opportunités offertes par les organoïdes intestinaux humains dans un contexte de médecine de précision et de médecine réparatrice.
- Published
- 2019
33. [Organoids: mini-organs at the service of biomedicine]
- Author
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Galzi, Jean-Luc, Jouault, Thierry, Amédée, Joëlle, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bioingénierie tissulaire (BIOTIS), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Organoids ,Tissue Culture Techniques ,Biomedical Research ,Drug Development ,[SDV]Life Sciences [q-bio] ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Drug Evaluation, Preclinical ,[CHIM]Chemical Sciences ,Animals ,Humans ,Medicine ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences - Abstract
International audience; L'approche globale multi-échelle du vivant est mise en oeuvre par les industries de la santé pour lever les verrous qu'elles rencontrent actuellement dans la découverte et le développement de nouvelles thérapies, ainsi que pour la médecine régénérative dans sa démarche de reconstruction d'organes. Un des goulets est celui de la prédictibilité limitée qu'offrent les systèmes animaux modèles dans les différents domaines du développement du médicament, de la médecine de précision, de la pharmaco génomique et de la médecine régénérative. Cette faible prédictibilité est une des explications d'un taux d'attrition important de molécules en développement, entre autres. Les systèmes modèles actuels sont mis en question et l'utilisation potentielle de substituts tissulaires, ou organoïdes, en complément des modèles animaux couramment utilisés est désormais largement prise en compte dans l'évaluation des candidats
- Published
- 2019
34. [Kidney organoids]
- Author
-
Clara, Steichen, Sébastien, Giraud, and Thierry, Hauet
- Subjects
Gene Editing ,Organoids ,Pluripotent Stem Cells ,Induced Pluripotent Stem Cells ,Drug Evaluation, Preclinical ,Animals ,Humans ,Cell Differentiation ,Kidney - Abstract
This review focus on kidney organoids derived from pluripotent stem cells, which become a real alternative to the use of in vitro cellular models or in vivo animals models. The comprehension of the key steps involved during kidney embryonic development led to the establishment of protocols enabling the differentiation of pluripotent stem cells into kidney organoids that are highly complex and organized structures, composed of various renal cell types. These mini-organs are endowed with major applications: the possibility to control iPSC genome (by selecting patients with specific disease or by genome editing) allows the generation of kidney organoïds which recapitulate important physiopathological mechanisms such as cyste formation in renal polycystic disease. Kidney organoids can also be used in high-throughput screening to fasten the screening of nephrotoxic/therapeutic compounds. Finally, kidney organoids have a huge interest in the context of tissue repair, which remains for now a challenging goal linked with technological barriers that need still to be overcome.
- Published
- 2019
35. [3D Tumor organoid models produced by cellular capsules technology CCT].
- Author
-
Recher G, Mombereau A, Boyreau A, Nassoy P, and Andrique L
- Subjects
- Alginates, Cancer-Associated Fibroblasts, Cell Communication, Cell Proliferation, Coculture Techniques methods, Epithelial-Mesenchymal Transition, Extracellular Matrix chemistry, Humans, Neoplasm Invasiveness, Tumor Cells, Cultured, Tumor Microenvironment, Cell Culture Techniques, Three Dimensional methods, Cell Encapsulation methods, Organoids, Spheroids, Cellular
- Abstract
Monolayer cultures of cell lines and derived-patient cells have long been the in vitro model of choice in oncology. In particular, these models have made it possible to decipher the mechanisms that determine tumor proliferation and invasion. However these 2D models are insufficient because they do not take into account the spatial organization of cells and their interactions with each other or with the extracellular matrix. In the context of cancer, there is a need to develop new 3D (tumoroid) models in order to gain a better understanding of the development of these pathologies but also to assess the penetration of drugs through a tissue and the associated cellular response. We present here the cell capsule technology (CCT), which allows the production of different tumoroid models: simple or more complex 3D culture models including co-culture of tumor cells with components of the microenvironment (fibroblasts, matrix, etc.). The development of these new 3D culture systems now makes it possible to propose refined physiopathological models that will allow the implementation of improved targeted therapeutic strategies., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
36. [Spheroids to organoids: Solid cancer models for anticancer drug discovery].
- Author
-
Alzeeb G, Corcos L, and Le Jossic-Corcos C
- Subjects
- Drug Screening Assays, Antitumor methods, Humans, Models, Biological, Neoplasms pathology, Precision Medicine, Tumor Cells, Cultured, Tumor Microenvironment, Antineoplastic Agents therapeutic use, Cell Culture Techniques, Three Dimensional methods, Drug Discovery, Neoplasms drug therapy, Organoids drug effects, Organoids pathology, Spheroids, Cellular drug effects, Spheroids, Cellular pathology
- Abstract
Cell culture is an important and necessary technology in oncology research. Currently, two-dimensional (2D) cell culture models are the most widely used, but they cannot reproduce the complexity and pathophysiology of tumors in vivo. This may be a major cause of the high rate of attrition of anticancer drugs entering clinical trials, the rate of new anticancer drugs entering the market being less than 5 %. One way to improve the success of new cancer drugs in the clinic is based on the use of three-dimensional (3D) cell culture models, more able to represent the complex environment and architecture of tumors. These 3D culture systems are also a powerful research tool for modeling the evolution of cancer from early stages to metastasis. Spheroids and organoids, the most adaptable models among 3D culture systems, are beginning to be used in pharmaceutical research and personalized medicine. In this article, we review the use of spheroids and organoids by highlighting their differences, discussing their impact on drug development, and looking at future challenges., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
37. [Normal organoids and their applications in cancer research].
- Author
-
Delom F, Le Morvan V, Robert J, and Fessart D
- Subjects
- Bronchi anatomy & histology, Carcinogenesis genetics, Cell Differentiation, Cell Self Renewal, Humans, Lung Neoplasms pathology, Neoplasms genetics, Precision Medicine, Tumor Cells, Cultured pathology, Biomedical Research, Cell Culture Techniques, Three Dimensional methods, Neoplasms pathology, Organoids pathology
- Abstract
Three-dimensional (3D) culture of organoids from primary cells (wild type) or tumoroids from tumor cells, is used to study the physiological mechanisms in vivo, in order to model normal or tumor tissues more accurately than conventional two-dimensional (2D) culture. The features of this 3D culture, such as the three-dimensional structure, the self-renewal capacity and differentiation are preserved and appropriate to cancer study since their cellular characteristics are very similar to in vivo models. Here, we summarize the recent advances in the rapidly evolving field of organoids and their applications to cancer biology, clinical research and personalized medicine., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
38. [Generating pancreatic islets organoids: Langerhanoids].
- Author
-
Papoz A, Clément F, Laporte C, Tubbs E, Gidrol X, and Pitaval A
- Subjects
- Humans, Insulin, Organoids, Insulin-Secreting Cells, Islets of Langerhans, Islets of Langerhans Transplantation
- Abstract
The extension of islet transplantation to a wider number of Type 1 diabetic patients is compromised by the scarcity of donors, the reduced ex vivo survival of pancreatic islets and the use of immunosuppressive treatments. Islets of Langerhans isolated from brain-dead donors are currently the only cell source for transplantation. Thus, it is crucial to find an alternative and an abundant source of functional insulin secreting cells not only for clinical use but also for the development of research dedicated to the screening of drugs and to the development of new therapeutic targets. Several groups around the world, including ours, develop 3D culture models as Langerhanoids that closely mimick human pancreatic islets physiology. In this review, we describe recent advances to mimic the pancreatic niche (extracellular matrix, vascularization, microfluidics) allowing better functionality of Langerhanoids., (© 2022 médecine/sciences – Inserm.)
- Published
- 2022
- Full Text
- View/download PDF
39. Effects of thrombin of human colic epithelium on organoids (3D ex vivo model)
- Author
-
Sébert, Morgane, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paul Sabatier - Toulouse III, Nathalie Vergnolle, Audrey Ferrand, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)
- Subjects
Organoids ,Thrombine ,Colon ,Thrombin ,Organoïdes ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,HCS ,PARs - Abstract
Thrombin, a serine protease known for its role in the coagulation cascade, was described for its effects on the induction of apoptosis in colonic epithelial cell lines, through the activation of Protease Activated Receptors (PARs). However, the effects of thrombin on complex epithelial structures such as the human intestinal epithelium composed of different cell types and cells at different stages of differentiation, has never been investigated. A new cellular model, named organoid, enables to reconstitute a functional epithelium in 3-dimensions (3D), from human resections or biopsies, thanks to the self-renewal and differentiation properties of stem cells isolated from colonic crypts. The first objective of this thesis was to evaluate thrombin's effects on survival, proliferation, apoptosis and differentiation in human colonic epithelium, using the organoid model. Then, we aimed to determining the implication of PAR1 and PAR4 in the thrombin's effects. Thus, thrombin added (at low dose: 10mU/mL and higher dose: 50mU/mL) to organoid cultures from control patients, led to a decrease by half of metabolic activity and cell proliferation. These effects were blocked by the addition of a PAR1 antagonist. Apoptotic process was 8-fold higher in organoid cultures exposed to thrombin (both doses) and this effect was inhibited by the addition of a PAR1 or a PAR4 antagonist. As per epithelial differentiation, thrombin decreased the number of colonospheres (immature structures) favoring the increase of apoptotic structures and colonoids (budding structures considered as more mature). This effect was due to PAR1 and PAR4 activation as again, it was blocked both by PAR1 and PAR4 antagonist. Taken together, these results reveal that exogenous thrombin acts on apoptosis, proliferation and differentiation processes in complex human colonic epithelium. The use of this ex vivo model will allow to compare pathological versus normal organoid cultures, but also to test the effects of pharmacological approaches and new treatment options directly in cultured human tissues. Thus, the 2nd part of this thesis was to setup the best culture conditions and the best imaging conditions to perform a robust and reproducible screening approach, HCS (High-Content Screening), using organoid cultures. Culture conditions in 96-well plates were set up and allowed to acquire images with the HCS system. Operetta HCS coupled to an analysis software (Harmony, PerkinElmer) was used to develop a specific program enabling the recognition of organoids, their counting, their classification according to their differentiation status and enabling to follow organoid growth in cultures. To sum up, the work performed allowed to highlight the effects of thrombin on metabolic status, apoptosis and differentiation of human colon epithelium, using an ex vivo 3D organoid model. The use this model nicely completed epithelial cell line approaches, offering an integrated view of the complex behavior of human epithelium. The HCS approach initiated within this thesis should allow the automated analysis of a number of drugs and treatments. It should help our understanding of epithelial pathologies and the testing of new therapeutic approaches.; La thrombine, une protéase à sérine connue pour être l'acteur clé de la cascade de coagulation, a été décrite pour réguler les processus apoptotiques au niveau du côlon via l'activation de récepteurs activés par des protéases ou PARs (Protease-Activated Receptors). Cependant, les effets de la thrombine sur la cellule épithéliale colique n'ont été étudiés qu'en utilisant des lignées cellulaires. Les conséquences d'une exposition à différentes doses de thrombine sur un épithélium complexe, composés de différents types cellulaires plus ou moins différenciés sont inconnues à ce jour. Un nouveau modèle cellulaire, nommé organoïde, permet de reconstituer un épithélium colique fonctionnel en 3-dimensions (3D) à partir de résections ou de biopsies humaines, et ce, grâce aux capacités d'auto-renouvellement et de différenciation des cellules souches issues des cryptes coliques. Le 1er objectif de ma thèse a été d'évaluer les effets de la thrombine sur la survie, la prolifération, l'apoptose et la différenciation de l'épithélium colique humain, en utilisant le modèle organoïde. Puis, de déterminer l'implication des récepteurs PAR1 et PAR4 activés par la thrombine dans ces effets. Ainsi, l'ajout de thrombine (à faible dose : 10mU/mL et à forte dose : 50mU/mL) sur une culture d'organoïdes établis à partir de tissus colorectaux normaux entraîne une diminution de moitié de l'activité métabolique et de la prolifération cellulaire. Ces effets sont bloqués en présence d'un antagoniste de PAR1. Le processus apoptotique est, cependant, augmenté d'un facteur 8 en réponse à la thrombine (aux deux doses). Ce processus est inhibé en présence d'antagoniste de PAR1 ou de PAR4. Concernant la différenciation épithéliale, la thrombine diminue le nombre de colonosphères (structures immatures), au profit d'une augmentation du nombre de structures apoptotiques et de colonoïdes (structures plus matures présentant des néo-cryptes). Cet effet est dû à l'activation à la fois de de PAR1 et de PAR4 dans les cellules épithéliales coliques. Mes résultats démontrent que la thrombine exogène agit sur les processus d'apoptose, de prolifération et de différenciation sur un épithélium complexe, issu de la culture de tissus humains. L'utilisation de ce modèle ex vivo permet de comparer les organoïdes pathologiques et normaux, voire de tester les effets d'approches pharmacologiques et de nouveaux médicaments sur ces cultures. Ainsi, la 2nde partie de ce travail de thèse a été d'aborder la mise en place des conditions de culture et d'imagerie nécessaires pour réaliser un screening à haut débit robuste et reproductible, HCS (High-Content Screening), appliquée aux organoïdes. Les conditions de culture d'organoïdes en plaques 96-puits ont été mises au point de même que les conditions permettant d'acquérir des images répondant aux critères nécessaires pour une analyse via un système HCS. Le système Operetta HCS couplé au logiciel d'analyse Harmony (PerkinElmer) a été utilisé pour mettre en place une procédure d'analyse permettant de reconnaître les organoïdes, de les dénombrer, de les classer selon leur état de différenciation et de suivre leur croissance tout au long de la culture. Pour conclure, ces travaux de thèse ont permis de mettre en évidence les effets de la thrombine sur l'état métabolique, l'apoptose et la différenciation de l'épithélium colique humain, grâce au modèle 3D ex vivo d'organoïdes colorectaux. L'utilisation de ce modèle complète les approches jusque-là effectuées dans des modèles de lignées de cellules épithéliales, proposant une vision intégrée du comportement d'un épithélium complexe humain. L'approche HCS initiée lors de ces travaux de thèse pourrait permettre d'analyser de façon robuste et automatisée dans ce modèle, les effets d'autres composés et avoir ainsi un impact majeur sur notre compréhension des pathologies épithéliales et sur les tests de nouvelles approches thérapeutiques.
- Published
- 2018
40. [Hepatic organoids: What are the challenges?]
- Author
-
Luce E, Messina A, Caillaud A, Si-Tayeb K, Cariou B, Bur E, Dubart-Kupperschmitt A, and Duclos-Vallée JC
- Subjects
- Cell Differentiation, Hepatocytes, Humans, Liver, Organoids, Induced Pluripotent Stem Cells, Pluripotent Stem Cells
- Abstract
The study and understanding of liver organogenesis have allowed the development of protocols for pluripotent stem cells differentiation to overcome the lack of primary cells, providing an almost unlimited source of liver cells. However, as their differentiation in conventional 2D culture systems has shown serious limits, hepatic organoids derived from human pluripotent stem cells represent a promising alternative. These complex and organized structures, containing one or more cell types, make it possible to recapitulate in vitro some of the organ functions, thus enabling numerous applications such as the study of the liver development, the mass production of functional liver cells for transplantation or the development of bioartificial livers, as well as the in vitro modeling of hepatic pathologies allowing high throughput applications in drug screening or toxicity studies. Economic and ethical issues must also be taken into account before using these organoids in therapeutic applications., (© 2021 médecine/sciences – Inserm.)
- Published
- 2021
- Full Text
- View/download PDF
41. [An organoid biobank to help children with kidney cancer].
- Author
-
Grinberg S, Rous I, and Cartry J
- Subjects
- Biological Specimen Banks, Child, Humans, Precision Medicine, Kidney Neoplasms genetics, Organoids
- Published
- 2021
- Full Text
- View/download PDF
42. [Progress in prostate cancer study: 3D cell culture enables the ex vivo reproduction of tumor characteristics]
- Author
-
Victor, Tostivint, Claire, Racaud-Sultan, Mathieu, Roumiguié, Michel, Soulié, Xavier, Gamé, and Jean-Baptiste, Beauval
- Subjects
Male ,Organoids ,Spheroids, Cellular ,Cell Culture Techniques ,Tumor Cells, Cultured ,Tumor Microenvironment ,Humans ,Prostatic Neoplasms - Abstract
Despite new therapeutics options, Prostate Cancer (PCa) remains a public health challenge because of its high incidence and mortality. Limits in PCa research come from the lack of in vitro and in vivo models that mimic the human disease. Currently, 2D in vitro tissue culture models of PCa are widely used but they present numerous limits. They do not reproduce cellular morphology, tissue architecture, inter-patients and intratumor heterogeneity. Furthermore, they lack two key components of PCa tumors, the tumoral microenvironment and the cancer stem cells. In vivo murine models of PCa cannot be representative of all the genetic alterations known in prostate tumors and they hardly reproduce the pathophysiology of human metastatic progression. Consequently, the physiology of these in vitro and in vivo models do not well represent patients tumors. 3D cell cultures overcome many of these limits by sharing morphologic characteristics with in vivo tumors as well as reproducibility of in vitro models. 3D models of PCa include spheroids derived from tumor cell lines, and organoids, derived from patient. In 3D cell cultures, cell fitness is maintained, the physiological cells-cells and cell-matrix interactions are restored and an extracellular matrix surrounds the cells. Organoids, generated from PCa primary tumors or metastases, allow studies on cancer stem cells and their microenvironment. Moreover, organoids retain genetic integrity of PCa tumors. PCa organoid model is an innovative tool that offers great perspectives of therapeutic screening. In the future, organoids generated from patients' biopsies may also lead to personalized medicine.
- Published
- 2016
43. [News drugs and evolution towards personalized treatment for cystic fibrosis].
- Author
-
Boboli H, Pirson J, Seghaye MC, and Kempeneers CC
- Subjects
- Cystic Fibrosis Transmembrane Conductance Regulator, Genotype, Humans, Mutation, Organoids, Cystic Fibrosis drug therapy, Precision Medicine
- Abstract
Cystic fibrosis is a genetic disorder responsible for the production of a defective transmembrane protein. In recent years, new protein modulators have been developed. They aim to treat the underlying cause of the disease. The results on the biomarkers of the function of the CFTR protein and on the clinical outcomes are very encouraging. However, there is an individual heterogeneity in the response to modulators within a same genotype. Furthermore, clinical trials focus on the most common mutations in the CFTR gene, in particular DF508. Intestinal organoids, a new model of ex vivo study, could offer a quick approach to increase access to effective treatment for all patients with cystic fibrosis regardless of their CFTR genotype. Organoids could enable personalized treatment of cystic fibrosis.
- Published
- 2020
44. Distribution of $sup 13$C and $sup 12$C isotopes in rat hepatic cells
- Author
-
Duchesne, J
- Published
- 1973
45. [Progress in prostate cancer study: 3D cell culture enables the ex vivo reproduction of tumor characteristics].
- Author
-
Tostivint V, Racaud-Sultan C, Roumiguié M, Soulié M, Gamé X, and Beauval JB
- Subjects
- Humans, Male, Organoids, Spheroids, Cellular, Tumor Cells, Cultured, Tumor Microenvironment, Cell Culture Techniques methods, Prostatic Neoplasms pathology
- Abstract
Despite new therapeutics options, Prostate Cancer (PCa) remains a public health challenge because of its high incidence and mortality. Limits in PCa research come from the lack of in vitro and in vivo models that mimic the human disease. Currently, 2D in vitro tissue culture models of PCa are widely used but they present numerous limits. They do not reproduce cellular morphology, tissue architecture, inter-patients and intratumor heterogeneity. Furthermore, they lack two key components of PCa tumors, the tumoral microenvironment and the cancer stem cells. In vivo murine models of PCa cannot be representative of all the genetic alterations known in prostate tumors and they hardly reproduce the pathophysiology of human metastatic progression. Consequently, the physiology of these in vitro and in vivo models do not well represent patients tumors. 3D cell cultures overcome many of these limits by sharing morphologic characteristics with in vivo tumors as well as reproducibility of in vitro models. 3D models of PCa include spheroids derived from tumor cell lines, and organoids, derived from patient. In 3D cell cultures, cell fitness is maintained, the physiological cells-cells and cell-matrix interactions are restored and an extracellular matrix surrounds the cells. Organoids, generated from PCa primary tumors or metastases, allow studies on cancer stem cells and their microenvironment. Moreover, organoids retain genetic integrity of PCa tumors. PCa organoid model is an innovative tool that offers great perspectives of therapeutic screening. In the future, organoids generated from patients' biopsies may also lead to personalized medicine., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
46. [Role and origin of the centriole]
- Author
-
M, Bornens
- Subjects
Organoids ,Animals ,Centrioles - Abstract
The centriole could constitute a system of inertia in the cell, providing the system of references controlling the movement of the cell. It would ensure equally the coherence of cell metabolism and its stability. The origin and functioning of the centriole would be linked to a singel physical phenomenon.
- Published
- 1978
47. [Ultrastructural study of the oviduct of the triton Pleurodeles waltlii Michah. III. Effect of 17 beta-estradiol on the differentiation of secretory cells of the middle oviduct in the immature female]
- Author
-
C, Boisseau
- Subjects
Organoids ,Mucous Membrane ,Time Factors ,Estradiol ,Mollusca ,Animals ,Golgi Apparatus ,Cell Differentiation ,Epithelial Cells ,Female ,Oviducts ,Ribosomes ,Epithelium - Published
- 1975
48. [Cells in the normal human periodontal ligament. An ultrastructural, histo-enzymological and immunocytochemical study on in vitro cultures]
- Author
-
G, Chomette, M, Auriol, D, Armbruster, H, Szpirglas, and J M, Vaillant
- Subjects
Adult ,Microvilli ,Histocytochemistry ,Periodontal Ligament ,Mitosis ,Alkaline Phosphatase ,Immunohistochemistry ,Organoids ,Microscopy, Electron, Scanning ,Humans ,Vimentin ,Collagen ,Oxidoreductases ,Cells, Cultured - Abstract
Four cellular cultures from explants of human periodontal ligament were studied. In these cultures, cells were fusiform or stellate with a high percentage (5 to 10%) of round mitotic cells. The scanning electron microscope confirmed the simultaneous presence of flat cells in interphase and cells in prophase with microvilli and long filipodes and of round mitotic cells with microvilli and blebs. Histoenzymology disclosed in these cells high activities in oxidative enzymes and leucine aminopeptidase. Furthermore some cells showed an alkaline phosphatase activity. Immunocytochemistry detected in most of these cells intermediate vimentin filaments and the presence of type I and III collagen irregularly distributed among these cells. In transmission electron microscopy the elongated cells presented a clear nucleus, numerous endocytosic vesicles, ribosomes and longitudinal filaments. Variations were noted, especially in the quantity and quality of cell secretions, the fibroblasts secreting either the two type I and III collagen or only type I. The rare cells assuming alkaline phosphatase activity were atypical in possibly being provided with osteogenic potential.
- Published
- 1987
49. [Coating of centrospheres by reticulum cisternae and formation of spindle residues in segmentation mitosis under the action of an antitubulin substance: nocodazole]
- Author
-
P, Sentein and Y, Atès
- Subjects
Zygote ,Mitosis ,Endoplasmic Reticulum ,Microtubules ,Triturus ,Chromosomes ,Organoids ,Animals ,Benzimidazoles ,Female ,Chloral Hydrate ,Anaphase ,Colchicine ,Centrioles - Abstract
When cleaving eggs are treated by nocodazole the reticulum cisternae coat the centrospheres instead of the chromosomes, as normally occurs at the late anaphase. At the same time the spindle is reduced to a common mass or spindle remnant, constituted of unorientated and fragmented microtubules which embed the kinetochores, i. e. the star configuration of the chromosomes. This action is quite similar to that of chloralhydrate but is different from that of colchicine.
- Published
- 1979
50. [On the structure of the hypogastric ganglion in adult rats (author's transl)]
- Author
-
Y, Nouhouayi, I, Negulesco, and R, Coujard
- Subjects
Cell Nucleus ,Male ,Neurons ,Ganglia, Sympathetic ,Cell Membrane ,Prostate ,Rats, Inbred Strains ,Mitochondria ,Rats ,Organoids ,Microscopy, Electron ,Synapses ,Vacuoles ,Animals ,Lysosomes - Abstract
Histological and ultrastructural examination of the hypogastric ganglion in rat indicated three kinds of cells: - The principal neurons, sympathetic cells remarkable by size, distribution, nematosomes and ergastosomes, absence of synaptic vesicles. After purchasing of vacuoles they occur vacuolated neurons. - The small neurons which are not sympathoblasts. - Few S.I.F. cells containing numerous dense core vesicles. The innervation is a double one, it is afferent cholinergic type or a type with catecholamines secretion.
- Published
- 1981
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