Since organoids and MPS can mimic organ and tissue function in the laboratory, they are an invaluable tool for researchers trying to understand organ function and dysfunction under controlled conditions. At EMBL Barcelona, Maria Bernabeu, Talya Dayton, Miki Ebisuya, and Kristina Haase lead research groups that study cerebral malaria, cancer, spinal deformation, and microvascular dysfunction, respectively, using these systems.<\/p>\n\n\n\n
Maria Bernabeu and her team study cerebral malaria<\/strong>, a disease that causes around 400,000 deaths a year. Malarial parasites stick to small blood vessels in the brain (microvasculature) releasing toxins that disrupt the blood-brain barrier, causing vessel blockage and brain swelling. This makes cerebral malaria one of the most fatal malaria complications with a 20% mortality rate even after antimalarial drug administration. <\/p>\n\n\n\n \u201cCurrent knowledge of cerebral malaria is based primarily on autopsy analysis, because of limitations of available animal models,\u201d said Viola Introini, postdoc in the Bernabeu Lab. \u201cWe cannot study disease onset and progression in humans because of ethical reasons. As an alternative, our group engineers 3D human brain microvessel models that incorporate crucial cells like pericytes and astrocytes to better mimic the blood-brain barrier. They can be used to study vascular dysfunctions caused by parasite infection in physiological conditions, aiming to provide a holistic understanding of cerebral malaria.\u201d<\/p>\n\n\n\n The COVID-19 pandemic has also shown us how important it is to understand the development of infectious diseases, and organoids and MPS devices can be incredibly helpful. During the pandemic and using both MPS devices and organoids, researchers across the world could replicate interactions between SARS-CoV-2 and organs like lungs, kidneys, or blood vessels. In addition, they could study immune responses and assess the effectiveness of therapies. <\/p>\n\n\n\n At EMBL Barcelona, the Haase and Bernabeu group joined forces to study how SARS-CoV-2, the novel coronavirus, produces microvascular inflammation<\/strong>. <\/p>\n\n\n\n \u201cResults from this project can help us to identify how SARS-CoV-2 travels through the human body and whether or not existing drugs can reduce the impact of severe COVID-19, and may provide evidence for new targets to treat the disease,\u201d said Marina Fortea, a joint postdoc in the Bernabeu and Haase groups.<\/p>\n\n\n\n In addition to studying diseases and performing drug screening and toxicity assays, organoids and MPS can be developed into assays used in personalised medicine. These technologies can be used to explore the effects of drugs in individual patients, using patient-derived tissue. Nowadays, researchers can generate successful organoids from almost every patient biopsy, and this holds great hope for personalised medicine. <\/p>\n\n\n\n Group Leader Talya Dayton generates lung organoids from patient-derived tumour tissue to study cancer<\/strong>. Her group also generates organoids from healthy tissue, and this allows them to compare healthy tissue and cancer tissue.<\/p>\n\n\n\n \u201cThe fact that we can generate organoids from healthy cells and tumour cells in the same defined in vitro<\/em> system means that we can grow and study cancers across the entire existing range of malignancy,\u201d said Dayton. According to her, while traditional 2D cell lines can usually only be grown from highly aggressive cancers, organoids can be grown from even very early cancers, and this allows scientists to use this system to study how early cancers can become more malignant and highly aggressive. <\/p>\n\n\n\n \u201cIn our lab, we use organoids and genetic engineering to recapitulate the transition from healthy cell to<\/em> early cancer cell to<\/em> highly aggressive cancer that is the basis of cancer formation and progression. Using this, we can try to predict therapeutic strategies that can either prevent this transition from happening or that can reverse it,\u201d added Dayton. <\/p>\n\n\n\n At their heart, organoids and MPS devices are simplified three-dimensional in vitro <\/em>structures that mimic organ and tissue function. They can be created using stem cells, patient cells, or tissue samples and can be designed to simulate human physiology better than traditional 2D cell culture. In the case of MPS, these devices can mimic critical aspects of organs such as mechanical cues, e.g. blood flow, tissue stretch, or hydrostatic pressure.<\/p>\n\n\n\n \u201cAlthough 2D cell culture systems offer a high degree of flexibility and reproducibility, they do not fully capture the 3D complexity that cells experience in vivo \u2013 <\/em>thereby limiting their ability to recapitulate tissue and organ function,\u201d said Akinola Akinbote, PhD student at the Haase Group. \u201cIn comparison, MPS have the potential to better approximate the in vivo<\/em> environment by recapitulating multicellular 3D arrangement and the extracellular microenvironments in vitro<\/em>,\u201d <\/p>\n\n\n\n Akinbote\u2019s project seeks to harness human induced pluripotent stem cell technologies and microfluidics to generate perfusable cardiac-specific vascularised tissues<\/strong> \u2013 essentially mimicking human heart vessels on a matchbox-sized device. \u201cOur objective is to establish a representative model that enables the investigation of the coronary microvessels form and function in vitro<\/em>,\u201d said Akinbote. <\/p>\n\n\n\n The Ebisuya group studies how and why we humans are different from other species when it comes to embryonic development. To study this, Miki Ebisuya and her group work with organoids of different species and compare them. The researchers are already working on several mammalian species, including rabbits, cattle, and rhinoceroses, setting up a \u2018stem cell zoo\u2019 in the lab.<\/p>\n\n\n\n \u201cOur next project will focus on creating somitoids, from different species. Somitoids are organoids that mimic the precursor structures that give rise to the spinal column form during human embryonic development. We would like to measure the cell proliferation and cell migration speed of somitoids from different mammals to establish what and how somitogenesis is different among species,\u201d said Ebisuya.<\/p>\n\n\n\n MPS devices differ in size and design. Ranging from approximately the size of a USB memory stick to that of a credit card, they vary depending on need and usage. At EMBL Barcelona, one example that utilises such flexibility is the placenta-on-chip<\/strong> system developed by Marta Cherubini, postdoc in the Haase Group.<\/p>\n\n\n\n \u201cWe use a small device made from a flexible polymer with a central port where we grow cells to create a placental barrier,\u201d said Cherubini. \u201cWith the right nutrients and environment, cells spontaneously form vessels inside the chip. Around that port, there are several channels that allow us to supply fluids and molecules to the cells and analyse fetal-like vascular development.\u201d <\/p>\n\n\n\n A critical aspect of performing successful research with MPS is to be able to develop your own devices, tailored to the needs of the project. EMBL Barcelona has led a project on campus to be able to fabricate such tools \u2013 a 'maker-space' or collaborative place, with equipment to design and produce tools, from macro to micro scales. This space is called the micro Fabrication Laboratory \u2013 \u00b5FabLab<\/strong> \u2013 and is now open for the whole PRBB community.<\/p>\n\n\n\n \u201cThe advantage of using laser cutters, 3D printers, and CNC milling machines is that you can design small parts and generally fabricate them in an afternoon,\u201d said Kristina Haase, Group Leader at EMBL Barcelona and one of the main forces behind the creation of the \u00b5FabLab. \u201cThis is a huge advantage of prototyping \u2013 being able to make several iterations of a design quickly to optimise it for your needs and get it rapidly to the lab for biological experiments.\u201d<\/p>\n\n\n\n Over the last 20 years, researchers have developed several types of organoids with strong resemblance to in vivo<\/em> organs. However, organoid generation can be a lengthy process in some cases, and has relatively low throughput. The challenges of this field are somewhat related to the complexity of biology itself.<\/p>\n\n\n\n Building an MPS model presents the first challenge. Researchers need to capture the level of biological complexity and accuracy of the organ, as well as its size and its fluid volume. In organoids and MPS models, there are several types of cells that coexist in the same space. Creating and maintaining such cell heterogeneity is a challenge. At EMBL Barcelona, many MPS models include vasculature, which is a dynamic and complex system. In addition, obtaining sufficient cells to perform experiments is not always a straightforward process, especially if these are patient-derived.<\/p>\n\n\n\n In spite of the above-mentioned challenges, these 3D miniaturised organs and devices present many benefits: they provide researchers with greater insights into human physiology, they can better approximate the in vivo<\/em> environment of organs, and they can be created with patient-derived tissue. <\/p>\n\n\n\n Recently, the US Food and Drug Administration (FDA) approved the use of microfluidic devices for drug testing, ending a federal mandate from 1938 that obliged experimental drugs to be tested on animals before they were used in human clinical trials. This new law opens the door to new technologies that aim to reproduce human physiology in vitro<\/em> as a means of effective preclinical research.<\/p>\n\n\n\n There is also growing recognition from industry that these techniques are suitable for preclinical drug screening, tissue regeneration, and toxicology\/safety evaluation. Advances in this field, including those led by EMBL Barcelona, will therefore represent a reduction in animal testing, more targeted drug evaluation, and the development of personalised medicine.<\/p>\n","post_title":"Organs-on-chip: new horizons for disease research","post_excerpt":"EMBL Barcelona researchers are studying how tissues develop in health and disease using organoids and 3D multicellular systems to mimic human organs and their functions.\n","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"organs-on-chip-new-horizons-for-disease-research","to_ping":"","pinged":"","post_modified":"2023-05-15 12:25:03","post_modified_gmt":"2023-05-15 10:25:03","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=58533","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"}],"embletc_main_story_subheading":" Groundbreaking technologies help researchers study disease development in context<\/p>\n","embletc_main_story_teaser":" EMBL Barcelona researchers are studying how tissues develop both in healthy and diseased states using organoids and 3D multicellular systems to mimic human organs and their functions.<\/p>\n","embletc_main_story_image":{"ID":58699,"id":58699,"title":"25042023_EMBLetc100th_Articlevisual","filename":"25042023_EMBLetc100th_Articlevisual-scaled.jpg","filesize":456758,"url":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/25042023_EMBLetc100th_Articlevisual-scaled.jpg","link":"https:\/\/www.embl.org\/news\/embletc\/issue-100\/attachment\/25042023_embletc100th_articlevisual\/","alt":"Science illustration representing research on organoids, organs-on-chip, and human health. The abstract composition shows several elements representing research into organoids and microphysiological systems, and their intertwined role in understanding health and disease.","author":"124","description":"Science illustration representing research on organoids, organs-on-chip, and human health. The abstract composition shows several elements representing research into organoids and microphysiological systems, and their intertwined role in understanding health and disease. Credit: Joana Gomes Campos de Carvalho\/EMBL","caption":"Science illustration representing research on organoids, organs-on-chip, and human health. The abstract composition shows several elements representing research into organoids and microphysiological systems, and their intertwined role in understanding health and disease. Credit: Joana Gomes Campos de Carvalho\/EMBL","name":"25042023_embletc100th_articlevisual","status":"inherit","uploaded_to":58531,"date":"2023-05-03 09:55:45","modified":"2023-05-04 18:13:19","menu_order":0,"mime_type":"image\/jpeg","type":"image","subtype":"jpeg","icon":"https:\/\/www.embl.org\/news\/wp-includes\/images\/media\/default.png","width":2560,"height":1536,"sizes":{"thumbnail":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/25042023_EMBLetc100th_Articlevisual-150x150.jpg","thumbnail-width":150,"thumbnail-height":150,"medium":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/25042023_EMBLetc100th_Articlevisual-300x180.jpg","medium-width":300,"medium-height":180,"medium_large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/25042023_EMBLetc100th_Articlevisual-768x461.jpg","medium_large-width":768,"medium_large-height":461,"large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/25042023_EMBLetc100th_Articlevisual-1024x614.jpg","large-width":1024,"large-height":614}},"embletc_main_story_hero":{"ID":58697,"id":58697,"title":"20230428_Hero_EMBLetc","filename":"20230428_Hero_EMBLetc-scaled.jpg","filesize":189229,"url":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/20230428_Hero_EMBLetc-scaled.jpg","link":"https:\/\/www.embl.org\/news\/embletc\/issue-100\/attachment\/20230428_hero_embletc\/","alt":"","author":"124","description":"","caption":"","name":"20230428_hero_embletc","status":"inherit","uploaded_to":58531,"date":"2023-05-03 09:50:40","modified":"2023-05-03 09:50:40","menu_order":0,"mime_type":"image\/jpeg","type":"image","subtype":"jpeg","icon":"https:\/\/www.embl.org\/news\/wp-includes\/images\/media\/default.png","width":2560,"height":853,"sizes":{"thumbnail":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/20230428_Hero_EMBLetc-150x150.jpg","thumbnail-width":150,"thumbnail-height":150,"medium":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/20230428_Hero_EMBLetc-300x100.jpg","medium-width":300,"medium-height":100,"medium_large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/20230428_Hero_EMBLetc-768x256.jpg","medium_large-width":768,"medium_large-height":256,"large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/04\/20230428_Hero_EMBLetc-1024x341.jpg","large-width":1024,"large-height":341}},"embletc_other_stories":[{"ID":58535,"post_author":"124","post_date":"2023-05-15 12:00:00","post_date_gmt":"2023-05-15 10:00:00","post_content":"\n EMBLetc.<\/em> began its journey as a black-and-white printed newsletter in 1998, with the goal of providing \u201cnews about services, staff, science and society\u201d to EMBL staff and alumni. It was created by EMBL\u2019s Office of Information and Public Affairs (which later became the EMBL Communications office) and acted for many years as a one-stop shop for news, announcements, essays, opinions, and trivia related to EMBL\u2019s research and its people. <\/p>\n\n\n\n In recent years, EMBLetc.<\/em> has grown into an important channel for communicating the impact of EMBL\u2019s activities to the wider community in our member states as well as globally. During this time, it has passed through the able hands of various editors, including Sarah Sherwood, Charlotte Otter, Vienna Leigh, Adam Gristwood, Chloe Cross, Ed Dadswell, Oana Stroe, and Ivy Kupec. <\/p>\n\n\n\n It has also undergone many transformations, both in content and format. From the very early issues that were both personal and informal, directed primarily towards staff and alumni, it has evolved into a dazzling showcase of the activities and achievements of the institute and its people on various fronts, gaining a global readership and aided by the creation of new complementary internal communication channels. In terms of format, for EMBL\u2019s 40th anniversary in 2014, it was redesigned as a biannual magazine<\/a>, and with the 99th issue<\/a> that came out in November 2022, it became a fully digital publication, in line with EMBL\u2019s current sustainability initiatives. <\/p>\n\n\n\n On the occasion of EMBLetc.\u2019s<\/em> 100th issue, we took a quick look at the most recent 24 years of the organisation\u2019s history through the lens of its issues. And we found a set of common themes that came up again and again in its pages. <\/p>\n\n\n\n As research highlights in all 99 issues of EMBLetc. <\/em>show, EMBL is a world leader in cutting-edge life science research, pushing the boundaries of both fundamental and applied research to reveal exciting insights about how organisms function. Here are a few examples of EMBL\u2019s groundbreaking science from the last 24 years.<\/p>\n\n\n\n Two of EMBL\u2019s key missions are to offer vital services to scientists in the member states and the world and to train scientists, students, and visitors at all levels. As the following clippings show, this is something that EMBL has achieved and encouraged right from its early days. <\/p>\n\n\n\n Another EMBL mission is to coordinate and integrate European life science research, by stablishing links and initiating collaborative projects between scientists in Europe and the wider world. As these clippings from past EMBLetc. issues show, our many collaborations, partnerships, and connections are among our biggest strengths. <\/p>\n\n\n\n In addition to core funding from its member states, EMBL has been repeatedly successful in attracting monetary support from those who believe in its mission and using such funding to expand the range of its many contributions to the scientific community. Here are a few examples. <\/p>\n\n\n\n EMBL\u2019s fourth mission is to actively engage in technology transfer and industry relations. Among other programmes, this includes the EMBL corporate partnership programme, the EMBL-EBI industry programme, and technology transfer via EMBLEM, an affiliate and the commercial arm of EMBL. The following clippings demonstrate some of the early roots of this mission. <\/p>\n\n\n\n![\"Microscope](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/05\/Bernabeu_AVG_Vessel-1-HBMEC-VE-cad-tx-red-and-astrocytes-GFAP-488-004.nd2-RGB.jpg\")
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DIY: tailor-made devices in-house<\/strong><\/h2>\n\n\n\n
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The future of organoid technologies<\/strong><\/h2>\n\n\n\n
1. EMBL has always been a centre for great science\u2026<\/strong><\/h2>\n\n\n\n
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<\/a>2. \u2026 and for state-of-the-art services and training<\/strong><\/h2>\n\n\n\n
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<\/a>3. We take pride in our partnerships\u2026<\/strong><\/h2>\n\n\n\n
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<\/a>4. \u2026 and in those who support our missions with funding<\/strong><\/h2>\n\n\n\n
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<\/a>5. We support technology transfer, industry partnerships, and translational research<\/strong><\/h2>\n\n\n\n
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