Littérature scientifique sur le sujet « Multi-organ platform »

Translational Organ-on-Chip Platform (TOP) is a multi-institutional effort to develop an open platform for automated organ-on-chip culture that actively facilitates the integration of components from various developers.

Direct detection and analysis of biomolecules and cells in physiological microenvironment is urgently needed for fast evaluation of biology and pharmacy. The past several years have witnessed remarkable development opportunities in vitro organs and tissues models with multiple functions based on microfluidic devices, termed as “organ-on-a-chip”. Briefly speaking, it is a promising technology in rebuilding physiological functions of tissues and organs, featuring mammalian cell co-culture and artificial microenvironment created by microchannel networks. In this review, we summarized the advances in studies of heart-, vessel-, liver-, neuron-, kidney- and Multi-organs-on-a-chip, and discussed some noteworthy potential on-chip detection schemes.

3034 Background: A rapid, low-cost, sensitive, multi-cancer early detection (MCED) test would be transformational in the diagnostics field. Earlier cancer detection and instigation of treatment can increase survival rates. An effective test must accurately identify the small proportion of patients with typically non-specific symptoms who actually have cancer. Such symptoms don’t easily segregate by organ system, necessitating a multi-cancer approach. Methods: In this large-scale study ( n = 2094 patients) we applied the Dxcover Cancer Liquid Biopsy to differentiate cancer against non-cancer, as well as organ specific tests to identify cancers of the brain, breast, colorectal, kidney, lung, ovary, pancreas, and prostate. The test uses Fourier transform infrared spectroscopy to analyze all macromolecules in a minute volume of patient serum, and machine learning to build a classifier of the resultant spectral profiles for calling the likelihood of cancer. Results: For the overall cancer classification, our model achieved 90% sensitivity with 61% specificity when tuned for sensitivity, with detection rates of 93% for stage I, 84% for stage II, 92% for stage III and 95% for stage IV. We also tuned for maximum sensitivity or specificity, whilst the other statistic was fixed above a minimum value of 45%. This resulted in 94% sensitivity with 47% specificity, and 94% specificity with 48% sensitivity, respectively. For organ specific cancer classifiers area under the curve values were calculated for all cancers: brain (0.90), breast (0.74), colorectal (0.91), kidney (0.91), lung (0.90), ovarian (0.85), pancreatic (0.81) and prostate (0.85). Conclusions: Cancer treatment is often more effective when given earlier and this low-cost strategy can facilitate the requisite earlier diagnosis. With further development, the Dxcover MCED test could have a significant impact on early detection of cancer, which is vital in the quest for improved survival and quality of life.

3034 Background: A rapid, low-cost, sensitive, multi-cancer early detection (MCED) test would be transformational in the diagnostics field. Earlier cancer detection and instigation of treatment can increase survival rates. An effective test must accurately identify the small proportion of patients with typically non-specific symptoms who actually have cancer. Such symptoms don’t easily segregate by organ system, necessitating a multi-cancer approach. Methods: In this large-scale study ( n = 2094 patients) we applied the Dxcover Cancer Liquid Biopsy to differentiate cancer against non-cancer, as well as organ specific tests to identify cancers of the brain, breast, colorectal, kidney, lung, ovary, pancreas, and prostate. The test uses Fourier transform infrared spectroscopy to analyze all macromolecules in a minute volume of patient serum, and machine learning to build a classifier of the resultant spectral profiles for calling the likelihood of cancer. Results: For the overall cancer classification, our model achieved 90% sensitivity with 61% specificity when tuned for sensitivity, with detection rates of 93% for stage I, 84% for stage II, 92% for stage III and 95% for stage IV. We also tuned for maximum sensitivity or specificity, whilst the other statistic was fixed above a minimum value of 45%. This resulted in 94% sensitivity with 47% specificity, and 94% specificity with 48% sensitivity, respectively. For organ specific cancer classifiers area under the curve values were calculated for all cancers: brain (0.90), breast (0.74), colorectal (0.91), kidney (0.91), lung (0.90), ovarian (0.85), pancreatic (0.81) and prostate (0.85). Conclusions: Cancer treatment is often more effective when given earlier and this low-cost strategy can facilitate the requisite earlier diagnosis. With further development, the Dxcover MCED test could have a significant impact on early detection of cancer, which is vital in the quest for improved survival and quality of life.

In the conventional culture systems in vitro, the challenging organoid approach have recently been overcome by the development of microfluidic Organ Chip models of human intestine. The potential future applications of Intestine-on-Chips in disease modelling, drug development and personalized medicine are leading research to identify and investigate limitations of modern chip-based systems and to focus the attention on the gut epithelium and its specific barrier function playing a significant role in many human disorders and diseases. In this paper, we propose and discuss the importance to implement a multi-parameter analysis on an engineered platform for developing an Epithelial Gut On Chip model.

L’urbanisation et la mondialisation sont des phénomènes de société qui multiplient et complexifient les sources de pollution. Parmi elles, la pollution atmosphérique impacte notablement la santé humaine à l’échelle mondiale de par son caractère transfrontière. L’appareil respiratoire est une voie d’absorption de nombreux xénobiotiques, sous forme de gaz, d’aérosols ou de nanoparticules. Une fois dans les voies respiratoires, les substances inhalées sont susceptibles d’interagir avec les cellules pulmonaires. Les mécanismes par lesquels des xénobiotiques inhalés induisent des dommages pulmonaires sont complexes, notamment en raison de l’hétérogénéité cellulaire des poumons. En raison de cette complexité, les modèles animaux constituent un outil de référence pour les études toxicologiques prédictives, cependant, dans le contexte européen de réduction de l’expérimentation animale (REACH, et les règles 3R), le développement de méthodes alternatives fiables est devenu une nécessité. Les modèles in vitro sont de bons candidats car plus simple et moins couteux à mettre en oeuvre que les modèles vivo et permettent de travailler avec des cellules ou des tissus d’origine humaine ce qui contribue à améliorer la pertinence des résultats. Cependant, l’extrapolation limitée du vitro au vivo est souvent liée à un manque de complexité des modèles, notamment en raison de l’absence de communication inter-organes. Les technologies des multi-organes sur puce cherchent à surmonter ces limitations en connectant plusieurs organoïdes métaboliquement actifs au sein d’un même circuit de culture afin de reproduire des interactions de type systémiques. Dans ce contexte, nous décrivons un modèle permettant de connecter in vitro, par le biais de la microfluidique, une barrière pulmonaire (voie d’entrée des xénobiotiques inhalés) à un organe détoxifiant tel que le foie, afin d’évaluer la toxicité liée à un stress inhalatoire de façon plus systémique. Cette approche permet de considérer la biotransformation des composés inhalés et l’interaction inter-organes comme possible modulateurs de la toxicité. Le projet étant dans les premières phase de développement, la robustesse expérimentale était au coeur du projet. L’objectif principal était de prouver qu’une substance modèle était capable de transiter dans le dispositif, au travers des deux compartiments tissulaires, afin de pouvoir étudier la dynamique inter-organes poumon/foie en condition de stress xénobiotique. Le projet a été articulé en trois phases expérimentales : - Caractérisation des réponses biologiques spécifiques aux tissus pulmonaire et hépatique en réponse à un stress. La viabilité, la fonctionnalité et les activités métaboliques des monocultures ont été évaluées après exposition à une substance modèle. - Adaptation et préparation des monocultures aux conditions de co-culture afin de préserver la viabilité et la fonctionnalité des tissus. - Les compartiments pulmonaire et hépatique ont été cultivés jointement dans un circuit de culture microfluidique fermé. La co-culture a été exposée à une substance modèle à travers la barrière pulmonaire afin d’imiter un mode d’exposition inhalatoire. Les paramètres de viabilité et de fonctionnalité des tissus ont été évalué post-culture afin de mettre en évidence quelconque phénomène d’interaction inter-organe. La caractérisation du modèle de co-culture a été réalisé grâce à l’exposition d’un agent hépatotoxique de référence, largement étudié dans la littérature : l’acétaminophène aussi connu sous le nom de paracétamol (APAP). L’exposition à la barrière pulmonaire n’est pas physiologique mais permet d’observer quantitativement le passage et la circulation du xénobiotique à travers le dispositif car l’APAP interfère avec la viabilité et les performances métaboliques hépatique, permettant ainsi de vérifier que le compartiment hépatique peut avoir accès à l’exposition effectuée à travers la barrière pulmonaire
Urbanization and globalization are prevailing social phenomena that multiply and complexify the sources of modern pollution. Amongst others, air pollution has been recognized as an omnipresent life-threatening hazard, comprising a wide range of toxic airborne xenobiotics that expose man to acute and chronic threats. The defense mechanisms involved in hazardous exposure responses are complex and comprise local and systemic biological pathways. Due to this complexity, animal models are considered prime study models. However, in light of animal experimentation reduction (3Rs), we developed and investigated an alternative in vitro method to study systemic-like responses to inhalationlike exposures. In this context, a coculture platform was established to emulate interorgan crosstalks between the pulmonary barrier, which constitutes the route of entry of inhaled compounds, and the liver, which plays a major role in xenobiotic metabolism. Both compartments respectively comprised a Calu-3 insert and a HepG2/C3A biochip which were jointly cultured in a dynamically-stimulated environment for 72 hours. The present model was characterized using acetaminophen (APAP), a well-documented hepatotoxicant, to visibly assess the passage and circulation of a xenobiotic through the device. Two kinds of models were developed: (1) the developmental model allowed for the technical setup of the coculture, and (2) the physiological-like model better approximates a vivo environment. Based on viability, and functionality parameters the developmental model showed that the Calu-3 bronchial barrier and the HepG2/C3A biochip can successfully be maintained viable and function in a dynamic coculture setting for 3 days. In a stress-induced environment, present results reported that the coculture model emulated active and functional in vitro crosstalk that seemingly was responsive to high (1.5 and 3 mM) and low (12 and 24 μM) xenobiotic exposure doses. Lung/liver crosstalk induced modulation of stress response dynamics, delaying cytotoxicity, proving that APAP fate, biological behaviors and cellular stress responses were modulated in a broader systemic-like environment

COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and has emerged as a devastating pandemic. SARS-CoV-2 not only causes respiratory illness but also leads to impairment of multi-organ function. Scientists are racing to evaluate a range of experimental therapeutics to target COVID-19 systemically. The World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) are accelerating global research priorities to mobilize innovation towards diagnostics, treatments, and vaccines against COVID-19. In this scenario, information about appropriate organ-specific physiologically relevant models is critical to generate knowledge about the pathophysiology and therapeutic targeting of COVID-19. Human and animal organoids are providing a unique platform, demonstrating their applicability for experimental virology. This review provides a brief analysis of the available organoid models used to study and device strategies to combat COVID-19.

A cell culture microfluidic device has been developed to test the cytotoxicity of anticancer drugs while reproducing multi-organ interactions in vitro. Cells were cultured in separate chambers representing the liver and tumor. The two chambers were connected through a channel to mimick the blood flow. Glioblastoma (GBM) cancer cells (M059K) and hepatoma cells (HepG2) were cultured in the tumor and the liver chambers, respectively. The cytotoxic effect of cancer treatment drug Temolozomide (TMZ) was tested using this two chamber system. The experimental results showed that with the liver cells, the cancer cells showed much higher viability than those without the liver cells. This indicates that the liver metabolism has strong effect on the toxicity of the anticancer drug. The results demonstrated that the perfused two chamber cell culture system has the potential to be used as a platform for drug screening in a more physiologically realistic environment.