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Leurs efforts de recherche utiliseront les micro-tissus de foie humain InSphero 3D InSight™ afin de développer de nouveaux tests visant à prédire et évaluer certains mécanismes à l'origine des lésions hépatiques induites par les médicaments (LHIM) SCHLIEREN, SUISSE--(Marketwired - 28 avril 2017) - InSphero AG, le fournisseur de premier plan de modèles de cultures cellulaires 3D prêts à l'essai, a conclu un accord avec Pfizer Inc. ( : PFE), l'une des plus grandes sociétés biopharmaceutiques au monde, visant à développer un nouveau test de toxicologie prédictive utilisant les micro-tissus de foie humain InSphero 3D InSight™. Ce nouveau test mécanique in vitro visera à s'appuyer sur la sensibilité et la longévité accrue des modèles hépatiques 3D d'InSphero, ce qui pourrait permettre le multiplexage de plusieurs critères d'évaluation afin d'aider à détecter et prédire les mécanismes de toxicité des médicaments. Le Dr Jan Lichtenberg, PDG et cofondateur d'InSphero, a déclaré : " Notre modèle de foie en 3D permet aux chercheurs de mieux prédire la toxicité et les effets secondaires potentiels en utilisant des tests cellulaires plus pertinents du point de vue biologique. Ces modèles pourraient également aider à réduire la dépendance aux modèles animaux, qui ajoutent des coûts significatifs, retardent les délais de mise sur le marché et ne parviennent souvent pas à refléter avec précision la réponse humaine à un médicament. Nous avons déjà une relation de longue date avec Pfizer et ce nouvel accord va permettre le développement de tests dotés potentiellement d'encore plus d'utilité et de pouvoir prédictif pour le développement précoce de médicaments par Pfizer. " Le Dr Simon Messner, qui dirigera le projet pour InSphero, a ajouté : " La longévité et la nature organotypique des micro-tissus de foie humain 3D InSight™ sont en étroite corrélation avec celles du foie natif, exhibant une organisation cellulaire, une réponse à l'enzyme cytochrome P450 et une fonctionnalité métabolique appropriées. L'utilisation de ce modèle 3D pourrait découler sur des niveaux supérieurs d'exactitude et de précision concernant la prédiction in vitro de certains mécanismes de LHIM. " L'accord en question entre en vigueur en avril 2017 et implique les scientifiques aux États-Unis (Brunswick, Maine) et les installations à Schlieren (Suisse) d'InSphero, avec la contribution des scientifiques de Pfizer. Pour en savoir plus sur InSphero, veuillez consulter le site www.insphero.com. InSphero établit la norme en matière de tests in vitro pour les nouveaux médicaments au sein de l'industrie pharmaceutique et biotechnologique, grâce à des solutions complètes qui procurent davantage de confiance dans le processus décisionnel. Robuste et hautement pertinente du point de vue physiologique, sa suite de micro-tissus et services 3D InSight™ est utilisée par les plus grandes sociétés pharmaceutiques au monde pour améliorer l'efficacité de leur découverte de médicaments et de leurs tests d'innocuité. Les technologies et méthodes en instance de brevet d'InSphero permettent une production reproductible et à grande échelle de micro-tissus 3D sans échafaudage stimulés exclusivement par l'auto-assemblage cellulaire. La société se spécialise dans la fourniture de modèles 3D sur mesure et prêts à l'essai dérivés du foie, du pancréas et des tissus tumoraux, visant à fournir des données biologiques sans égal dans les domaines de la toxicologie du foie, des maladies métaboliques (ex. : diabètes et maladies hépatiques) et de l'oncologie (en particulier de l'immuno-oncologie). Prêts à l'essai, tous les micro-tissus d'InSphero sont validés de manière approfondie afin d'assurer la plus grande qualité, certifiés pour une utilisation dans une variété de tests et expédiés aux clients de la société à l'échelle mondiale au sein d'une plateforme optimisée par des sphéroïdes brevetée et facile d'utilisation. Forts d'une riche expertise dans le domaine des modèles 3D, les scientifiques d'application sur le terrain et le personnel de recherche de la société aident à assurer une intégration efficace ainsi qu'une formation sur place le cas échéant. Pour les clients qui préfèrent une stratégie d'approvisionnement avec une grande rapidité d'exécution, InSphero propose également des services de recherche sous contrat utilisant ses modèles de micro-tissus 3D. Les solutions InSphero 3D InSight™ donnent lieu à des conclusions significatives dans les revues à comité de lecture, par le biais d'initiatives industrielles collaboratives telles qu'EU-ToxRisk et HeCaToS, et ont été validées dans les plus grandes institutions gouvernementales et entreprises pharmaceutiques, chimiques et cosmétiques du monde. Fondée en 2009, la société privée a son siège social en Suisse et possède des filiales aux États-Unis et en Allemagne. Ses réalisations scientifiques et commerciales ont été reconnues par l'attribution de plusieurs prix nationaux et internationaux.


Patent
InSphero | Date: 2017-02-22

The present invention relates to a method of preparing cells for 3D tissue culture, which method comprises the steps of plating the cells on a suitable surface, optionally, checking for their capability to adhere to said surface, discarding the cells which have not adhered to said surface, detaching the adhered cells and transferring them into a 3D tissue culture process.


News Article | November 3, 2016
Site: www.marketwired.com

Dr. Olivier Frey honored by IQ Consortium and AAALAC International for work on microphysiological system to reduce animal-based drug testing SCHLIEREN, SWITZERLAND--(Marketwired - November 03, 2016) - Dr. Olivier Frey of InSphero AG has received the 2016 IQ Consortium and AAALAC International Global 3Rs Award for Europe, recognizing his pioneering work to integrate advanced 3D microtissue models into microphysiological systems (MPS) for in vitro drug testing. The award was presented to Dr. Frey at the AAALAC International Luncheon, held Wednesday, November 2 in conjunction with the American Association for Laboratory Animal Science (AALAS) 67th National Meeting in Charlotte, North Carolina. The Global 3Rs Awards recognize significant innovative contributions toward the advancement of ethical science through the 3Rs of animal research: refinement, replacement, or reduction of animal use. The award selection committee acknowledged Frey's work to advance MPS technology by interconnecting 3D microtissues derived from human tissues such as liver, heart, endocrine pancreas, or tumor using microfluidic channels to mimic a so-called "Body on a Chip" or BoC. Such systems serve as complex in vitro models used to assess the efficacy or toxicity of a drug in a multi-organ, animal-free system. Frey headed the research, conducted at the ETH Zurich and in collaboration with partners including InSphero, as part of the European Commission EU Body on a Chip (BoC) Project. The award specifically referenced work published in July of 2015 in the Journal of Biotechnology entitled "3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis," one of several peer-reviewed publications resulting from the project since 2014. Dr. Frey, who recently joined InSphero to serve as Microphysiological Systems Product Manager, stated "It is a tremendous honor to receive the 3Rs Award on behalf of all of the scientists who have collaborated on the project since its inception four years ago. As an innovator in the field of 3D cell culture, InSphero was a strong commercial partner and helped keep our work focused on developing a scalable, flexible technology." Dr. Jan Lichtenberg, CEO and co-founder of InSphero commented, "We are delighted to have a proven leader in microphysiological systems such as Olivier join the InSphero team. His expertise and familiarity with our advanced 3D tissue models will help us accelerate commercialization of the technology, focusing on pharmaceutical and chemical industry applications that reduce both drug development costs and the need for animal testing." For more information about InSphero, visit www.insphero.com. InSphero provides superior biological relevance to in vitro testing with its easy-to-use solutions for production, culture and assessment of organotypic 3D cell culture models. The company's patented technologies include the 3D Select™ Process (pending) and scaffold-free 3D cell culture plates that enable large-scale, reproducible production of a broad range of assay-ready 3D InSight™ Microtissues derived from liver, pancreas, tumor, heart, brain, and skin. These models and contract research services utilizing them help to identify promising drugs and toxic liabilities with greater predictive power at early development stages, enabling better pre-clinical decision making, saving development cost, and shortening time to market. InSphero technologies drive significant findings in peer-reviewed journals, through collaborative projects such as EU-ToxRisk and HeCaToS, and have gained validation in the world's largest government institutions and pharmaceutical, chemical and cosmetics companies. This 3D know-how is also being applied in the diagnostics field to aid development of personalized chemotherapeutic strategies for the treatment of cancer. Founded in 2009, the privately held company is headquartered in Schlieren, Switzerland with subsidiaries in the United States (Brunswick, ME) and Waldshut, Germany. It has been recognized for its scientific and commercial achievements with a number of national and international awards. Follow us on Twitter and LinkedIn, and visit www.insphero.com.


Patent
InSphero | Date: 2015-04-15

The present invention relates to a method of preparing cells for 3D tissue culture, which method comprises the steps of plating the cells on a suitable surface, optionally, checking for their capability to adhere to said surface, discarding the cells which have not adhered to said surface, detaching the adhered cells and transferring them into a 3D tissue culture process.


Schlieren, Switzerland, June 29, 2017 (GLOBE NEWSWIRE) -- In the most comprehensive evaluation of 3D spheroid hepatic cultures conducted to date, a publication co-authored by lead toxicologists and drug safety experts at AstraZeneca and Genentech revealed InSphero 3D InSight™ Human Liver Microtissues to be a more sensitive and highly specific in vitro model for predicting drug-induced liver injury (DILI) compared to 2D models. The study entitled, “Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury,” was published online Tuesday, June 13 in the journal Archives of Toxicology. Dr. William Proctor, Head of Investigative Toxicology at Genentech, and Alison Foster, Senior Scientist in the Drug Safety and Metabolism group at AstraZeneca, were co-first authors on the publication. 2D PHH assays have been the “gold-standard” model used for DILI testing, yet DILI still remains one of the leading sources for drug attrition, black box warnings, and post-market withdrawal of drugs. Thus, there is a growing need for better predictive tools to assess liver injury earlier in the drug development process. The authors note in the paper that, “3D models have shown promise in small sets of DILI compounds, but a more comprehensive retrospective study of DILI positive and negative drugs to test the predictive power of 3D models head to head with 2D PHH assays had not been performed.” The study determined that regardless of the threshold used, “Human Liver Microtissues demonstrated increased sensitivity in identifying known hepatotoxicants versus PHH, while specificity was consistent across both assays.” Microtissues also, “outperformed PHH in correctly classifying hepatotoxicants from different pharmacological classes of molecules.” Furthermore, the authors found that 3D microtissues displayed sufficient structural and functional characteristics to warrant exploratory studies to see if novel biomarkers used in the clinic could also be detected in vitro. Findings revealed that despite each microtissue consisting of ~1000 cells, the mechanistic and exploratory hepatotoxicity biomarkers miR-122, HMGB1, and α-GST could be detected in the culture supernatants, demonstrating that, “3D liver microtissues have the potential to recapitulate in vivo findings in vitro.” “This landmark study provides convincing, independent evidence that InSphero liver microtissues can help identify hepatotoxic drugs with greater sensitivity without sacrificing specificity, says InSphero Chief Executive Officer and Co-founder Dr. Jan Lichtenberg. “Having two of the world’s leading pharmaceutical companies collaborate to produce this thorough validation further confirms that our 3D models not only better reflect in vivo biology, but also deliver the reproducibility and scalability required to meet the early stage screening demands of large pharma. Our assay-ready 3D InSight™ models offer a cost-effective, turnkey solution that gives toxicologists greater confidence when characterizing risk in lead compound sets.” 3D InSight™ Human Liver Microtissues are a standardized primary human liver model developed by InSphero that display enhanced liver phenotype, metabolic activity, and stability over 28 days in culture, enabling long-term drug exposure studies not attainable with 2D hepatic models. For more information about InSphero 3D InSight™ Liver Microtissues and applications, visit www.insphero.com InSphero sets the standard for in vitro testing of novel drugs in the pharmaceutical and biotechnology industry with comprehensive solutions that provide greater confidence in decision making. Its robust and highly physiologically relevant suite of 3D InSight™ Microtissues and Services are used by major pharmaceutical companies worldwide to increase efficiency in drug discovery and safety testing. InSphero patent-pending technologies and methods enable large-scale, reproducible production of scaffold-free 3D microtissues driven solely by cellular self-assembly. The company specializes in delivering assay-ready and custom 3D models derived from liver, pancreas, and tumor tissues, to provide unrivalled biological insight into liver toxicology, metabolic diseases (e.g., diabetes and liver diseases), and oncology (with a focus on immuno-oncology). All InSphero microtissues are thoroughly validated to ensure the highest quality, certified for use in a variety of assays, and shipped globally to customers in a patented, easy-to-use spheroid-optimized platform, ready for research. Field application scientists and research staff with expertise in working with 3D models help ensure efficient integration and onsite training as needed. For customers who prefer an outsourcing strategy with fast turnaround, InSphero also offers contract research services utilizing their 3D microtissue models. InSphero 3D InSight™ solutions drive significant findings in peer-reviewed journals, through collaborative industry initiatives such as EU-ToxRisk and HeCaToS, and have gained validation in the world’s largest government institutions and pharmaceutical, chemical and cosmetics companies. Founded in 2009, the privately held company is headquartered in Switzerland, with subsidiaries in the United States and Germany. It has been recognized for its scientific and commercial achievements with several national and international awards. Follow us on Twitter and LinkedIn. A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/49b63be5-b99c-4789-82ec-255febd1bef4 A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/cd947eeb-93b5-4005-9072-76223d78942a A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/6f21ed8c-d6f6-4bd2-bf0e-f6e0e46ea6ff


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-33-2015 | Award Amount: 30.12M | Year: 2016

The vision of EU-ToxRisk is to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project will focus on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. EU-ToxRisk extensively integrates the adverse outcome pathway (AOP)-based toxicity testing concept. Therefore, advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of AOPs and key events (KE). The project combines in silico tools and in vitro assays by computational modelling approaches to provide quantitative data on the activation of KE of AOP. This information, together with detailed toxicokinetics data, and in vitro-in vivo extrapolation algorithms forms the basis for improved hazard and risk assessment. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fit-for-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The test systems will be combined to a flexible service package for exploitation and continued impact across industry sectors and regulatory application. The proof-of-concept for the new mechanism-based testing strategy will make EU-ToxRisk the flagship in Europe for animal-free chemical safety assessment.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.1.3-1 | Award Amount: 15.99M | Year: 2013

HeCaToS aims at developing integrative in silico tools for predicting human liver and heart toxicity. The objective is to develop an integrated modeling framework, by combining advances in computational chemistry and systems toxicology, for modelling toxic perturbations in liver and heart across multiple scales. This framework will include vertical integrations of representations from drug(metabolite)-target interactions, through macromolecules/proteins, to (sub-)cellular functionalities and organ physiologies, and even the human whole-body level. In view of the importance of mitochondrial deregulations and of immunological dysfunctions associated with hepatic and cardiac drug-induced injuries, focus will be on these particular Adverse Outcome Pathways. Models will be populated with data from innovative in vitro 3D liver and heart assays challenged with prototypical hepato- or cardiotoxicants; data will be generated by advanced molecular and functional analytical techniques retrieving information on key (sub-)cellular toxic evens. For validating perturbed AOPs in vitro in appropriate human investigations, case studies on patients with liver injuries or cardiomyopathies due to adverse drug effects, will be developed, and biopsies will be subjected to similar analyses. Existing ChEMBL and diXa data infrastructures will be advanced for data gathering, storing and integrated statistical analysis. Model performance in toxicity prediction will be assessed by comparing in silico predictions with experimental results across a multitude of read-out parameters, which in turn will suggest additional experiments for further validating predictions. HeCaToS, organized as a private-public partnership, will generate major socioeconomic impact because it will develop better chemical safety tests leading to safer drugs, but also industrial chemicals, and cosmetics, thereby improving patient and consumer health, and sustaining EUs industrial competitiveness.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.9.2 | Award Amount: 1.92M | Year: 2012

High attrition and failures rates in pharmaceutical and biotechnological drug development require a paradigm change towards more physiological human cell-based assays at an early time point in the process. The central idea of this proposal is to develop a versatile and reconfigurable pharmaceutical screening technology platform that relies on organotypic three-dimensional spherical microtissues. This platform will accommodate different types of human microtissues (tumor, brain, liver, heart etc.) and feature microfluidic interconnection between these tissues, thus mimicking the physiological context and conditions in a human body. Dosage of components or candidate drugs to, e.g., liver tissue will lead to the generation of metabolic products in the respective tissue compartment. These products then can be routed via the microfluidics to, e.g., connective tissue to assess the efficacy of the candidate drug and related adverse toxicological effects on the target tissue and functionally related tissues. This way, functional connectivity in a real body can be mimicked at the desired level of complexity, and the effects of drugs can be comprehensively assessed.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-16-2015 | Award Amount: 5.12M | Year: 2016

Self-renew and multilineage potential characterize stem cells. We have recently described that pancreas progenitor cells extracted from adult donors can be expanded long-term in vitro into 3D structures, which we have termed organoids. Pancreas organoids reproduce in vitro all the features of pancreas ductal epithelia, and have a limitless expansion potential. Thus, pancreas organoids promise to boost cell therapy of type 1 diabetes. We have recently observed that progenitor cells organoids preserve their genetic stability over a long time in culture. That represents an advantage, when compared to iPS or hES derived approaches, where genetic instability raises concerns for their future therapeutic applications. While progenitor organoids are promising for the future of cell therapy, bringing stem cell-based therapies to patients requires a reliable characterization (knowing what the cells do and how they do it, i.e. a phenotypic and molecular biology characterization), chemically well-defined culture media, and the capacity of mass-production under GLP/GMP conditions. The LSFM4LIFE consortium aims to the mass production of pancreas organoids for the cellular therapy of type 1 diabetes. The goals of the project are: (1) optimize growth and differentiation of human pancreas stem-cell organoids by employing phenotypic and molecular high-throughput screening (2) standardize the growth and differentiation of the organoids under well-defined biochemical conditions, and (3) achieve GLP/GMP-production of the human organoids for preclinical studies and phase I clinical studies. The close collaboration in the consortium between academic researchers and industry, as well as its cross-disciplinary composition, are essential to realize the goals of the project. The work packages of the project will have a technological impact in the form of patents and first market replication.


Patent
InSphero | Date: 2011-07-27

Multi-well plate (1) comprising a plurality of wells (4), a frame (5) for holding the plurality of wells (4) in a defined arrangement, a support element (50) for contacting a surface when the multi-well plate (1) is placed on the surface, wherein at least one well (4) of the plurality of wells is elastically displaceable relative to said support element (50).

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