{"id":2625,"date":"2023-02-07T14:07:18","date_gmt":"2023-02-07T05:07:18","guid":{"rendered":"https:\/\/bionauts.jp\/?p=2625"},"modified":"2023-02-17T13:42:24","modified_gmt":"2023-02-17T04:42:24","slug":"novel-nash-ex-vivo-model-using-hepatic-organoids-connected-to-bile-ducts-hbto","status":"publish","type":"post","link":"https:\/\/bionauts.jp\/?p=2625","title":{"rendered":"Novel NASH Ex vivo Model  using Hepatic Organoids Connected  to Bile Ducts (HBTO)"},"content":{"rendered":"<h3>Advantages<\/h3>\n<ul>\n<li>Quick induction of fatty liver pathology after construction of liver organoids (3-4 weeks)<\/li>\n<li>Easy and Real-time observation of free fatty acid (FFA) accumulation in hepatocytes<\/li>\n<li>Efficient profiling of multiple CYP activities affected by progression of fatty liver disease<\/li>\n<\/ul>\n<h3>Background &amp; Technology<\/h3>\n<p>This invention is a model for fatty liver diseases based on the Hepatobiliary Tubular Organoid (HBTO), a liver organoid with functional connections between hepatocytes and biliary epithelial cells, published in 2021 (Tanimizu N et al. Nat Commun 2021). Although several hepatobiliary organoids published before, HBTO is the only organoid in which the connection between hepatocytes and cholangiocytes can be visualized under a microscope. Give that some drug metabolites are transported to bile ducts in vivo, HBTO has the advantage of not only long-term expression of CYPs and albumin, but also of being equipped with a bile excretion channel, which enables analysis for metabolism of those drugs by collecting the excreted bile.<br \/>\nIn this study, we constructed an ex vivo fatty liver model with fat droplet accumulation in hepatocytes and activation of hepatic stellate cells, which are known to play an important role in liver injury, by adding FFA and lipopolysaccharides (LPS) to HBTOs.<\/p>\n<table style=\"border-collapse: collapse; width: 100%;\">\n<tbody>\n<tr>\n<td style=\"width: 100%;\"><img decoding=\"async\" loading=\"lazy\" class=\"alignright size-full wp-image-2627\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a.png\" alt=\"\" width=\"1637\" height=\"704\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a.png 1637w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a-300x129.png 300w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a-1024x440.png 1024w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a-768x330.png 768w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a-1536x661.png 1536w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a-1200x516.png 1200w\" sizes=\"(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 1362px) 62vw, 840px\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h3>Data<\/h3>\n<table style=\"border-collapse: collapse; width: 100%;\">\n<tbody>\n<tr>\n<td style=\"width: 100%;\"><img decoding=\"async\" loading=\"lazy\" class=\"alignright size-full wp-image-2628\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a2.png\" alt=\"\" width=\"1063\" height=\"368\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a2.png 1063w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a2-300x104.png 300w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a2-1024x354.png 1024w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/02\/ON-03088a2-768x266.png 768w\" sizes=\"(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 1362px) 62vw, 840px\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Left: Hepatic stellate cells within HBTO can be identified as Quiescent, Intermediate, and Activated states by staining for Desmin and \u03b1SMA.<\/p>\n<p>Right: Phase-contrast and fluorescence images of HBTOs cultured in the presence of FFA and LPS. Induction of hepatocyte death is not pronounced, but activation of hepatic stellate cells are induced. by addition of FFA and LPS.<\/p>\n<h3>Patent<\/h3>\n<p>\u30fbPending\u00a0 JP,US,DE<\/p>\n<h3>Applicant<\/h3>\n<p>\u30fbSapporo Medical University<\/p>\n<h3>Researcher<\/h3>\n<p>The University of Tokyo\u3000Center for Stem Cell Biology and Regenerative Medicine<br \/>\nAssociate Professor\u3000Naoki Tanimizu<\/p>\n<h3>Development Phase<\/h3>\n<p><strong>Current phase: <\/strong>Establishment of bile duct connected liver organoids and ex vivo fatty liver disease model with them, and completion of the histological observation and CYP profile analysis.<br \/>\n<strong>Next stage:<\/strong> 1) Construction of a cholestasis model using HBTOs containing human hepatocytes.<br \/>\n2)-1 Drug evaluation and exploratory screening using this fatty liver model (Collaboration)<br \/>\n2)-2 Commercialization of this fatty liver model and analysis for profile of CYP activities as a research tool (Collaboration)<\/p>\n<p>We are looking for partner companies interested in development and research collaboration mainly in 2) of the above. We would be happy to start with a detailed explanation and discussion of the technology.<\/p>\n<p>Project No: ON-03088a<\/p>\n<div class=\"control-gaia control-single_line_text-field-gaia field-5524858 control-show-gaia\">\n<div class=\"control-design-gaia\"><\/div>\n<\/div>\n<div class=\"control-gaia control-single_line_text-field-gaia field-5319149 control-show-gaia\"><\/div>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Advantages Quick induction of fatty liver pathology after construction of liver organoids (3-4 weeks) Easy and &hellip; <a href=\"https:\/\/bionauts.jp\/?p=2625\" class=\"more-link\"><span class=\"screen-reader-text\">&#8220;Novel NASH Ex vivo Model  using Hepatic Organoids Connected  to Bile Ducts (HBTO)&#8221; \u306e<\/span>\u7d9a\u304d\u3092\u8aad\u3080<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0},"categories":[1],"tags":[],"categories_of_inventions":[],"disease_categories___indication":[],"asset_type":[],"development_phase":[],"medicine":[102,99,104,121,112,96],"other_than_medicine":[140,138],"material":[],"engineering":[],"software_it":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2625"}],"collection":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2625"}],"version-history":[{"count":2,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2625\/revisions"}],"predecessor-version":[{"id":2630,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2625\/revisions\/2630"}],"wp:attachment":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2625"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2625"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2625"},{"taxonomy":"categories_of_inventions","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories_of_inventions&post=2625"},{"taxonomy":"disease_categories___indication","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdisease_categories___indication&post=2625"},{"taxonomy":"asset_type","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fasset_type&post=2625"},{"taxonomy":"development_phase","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdevelopment_phase&post=2625"},{"taxonomy":"medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedicine&post=2625"},{"taxonomy":"other_than_medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fother_than_medicine&post=2625"},{"taxonomy":"material","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmaterial&post=2625"},{"taxonomy":"engineering","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fengineering&post=2625"},{"taxonomy":"software_it","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fsoftware_it&post=2625"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}