{"id":107427,"date":"2023-06-14T16:01:12","date_gmt":"2023-06-14T20:01:12","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107427"},"modified":"2026-05-22T17:01:13","modified_gmt":"2026-05-22T21:01:13","slug":"rational-engineering-of-lung-alveolar-epithelium","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/","title":{"rendered":"Rational engineering of lung alveolar epithelium"},"content":{"rendered":"<p><strong>UVA Author:<\/strong> Karen Hirschi<br \/>\n<strong>Citation:<\/strong> Leiby KL, Yuan Y, Ng R, Raredon MSB, Adams TS, Baevova P, Greaney AM, Hirschi KK, Campbell SG, Kaminski N, Herzog EL, Niklason LE. Rational engineering of lung alveolar epithelium. NPJ Regen Med. 2023 Apr 28;8(1):22. doi: 10.1038\/s41536-023-00295-2. PMID: 37117221; PMCID: PMC10147714.<\/p>\n<p><strong>DOI:<\/strong> <a>https:\/\/doi.org\/10.1038\/s41536-023-00295-2<\/a><br \/>\n<strong>Pub-Med Number<\/strong>: 37117221<\/p>\n<hr \/>\n<section lang=\"en\" aria-labelledby=\"Abs1\" data-title=\"Abstract\" data-gtm-vis-polling-id-50443292_562=\"143\" data-gtm-vis-polling-id-50443292_563=\"144\" data-gtm-vis-recent-on-screen-50443292_562=\"190\" data-gtm-vis-first-on-screen-50443292_562=\"190\" data-gtm-vis-total-visible-time-50443292_562=\"6600\" data-gtm-vis-recent-on-screen-50443292_563=\"190\" data-gtm-vis-first-on-screen-50443292_563=\"190\" data-gtm-vis-total-visible-time-50443292_563=\"6600\">\n<div id=\"Abs1-section\" class=\"c-article-section\">\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<p>Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds in order to guide AEC2 behavior for epithelial regeneration. First, endothelial cells coordinate with fibroblasts, in the presence of soluble growth and maturation factors, to promote alveolar scaffold population with surfactant-secreting AEC2s. Subsequent withdrawal of Wnt and FGF agonism synergizes with tidal-magnitude mechanical strain to induce the differentiation of AEC2s to squamous type 1 AECs (AEC1s) in cultured alveoli, in situ. These results outline a rational strategy to engineer an epithelium of AEC2s and AEC1s contained within epithelial-mesenchymal-endothelial alveolar-like units, and highlight the critical interplay amongst cellular, biochemical, and mechanical niche cues within the reconstituting alveolus.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<div class=\"main-content\">\n<section data-title=\"Introduction\" data-gtm-vis-polling-id-50443292_563=\"168\" data-gtm-vis-recent-on-screen-50443292_563=\"3568\" data-gtm-vis-first-on-screen-50443292_563=\"3568\" data-gtm-vis-total-visible-time-50443292_563=\"3300\">\n<div id=\"Sec1-section\" class=\"c-article-section\"><\/div>\n<\/section>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>UVA Author: Karen Hirschi Citation: Leiby KL, Yuan Y, Ng R, Raredon MSB, Adams TS, Baevova P, Greaney AM, Hirschi KK, Campbell SG, Kaminski N, Herzog EL, Niklason LE. Rational engineering of lung alveolar epithelium. NPJ Regen Med. 2023 Apr 28;8(1):22. doi: 10.1038\/s41536-023-00295-2. PMID: 37117221; PMCID: PMC10147714. DOI: https:\/\/doi.org\/10.1038\/s41536-023-00295-2 Pub-Med Number: 37117221 Engineered whole lungs [&hellip;]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[22],"class_list":["post-107427","post","type-post","status-publish","format-standard","hentry","category-featured-publications","tag-intranet"],"acf":false,"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Rational engineering of lung alveolar epithelium - Department of Cell Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Rational engineering of lung alveolar epithelium - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"UVA Author: Karen Hirschi Citation: Leiby KL, Yuan Y, Ng R, Raredon MSB, Adams TS, Baevova P, Greaney AM, Hirschi KK, Campbell SG, Kaminski N, Herzog EL, Niklason LE. Rational engineering of lung alveolar epithelium. NPJ Regen Med. 2023 Apr 28;8(1):22. doi: 10.1038\/s41536-023-00295-2. PMID: 37117221; PMCID: PMC10147714. DOI: https:\/\/doi.org\/10.1038\/s41536-023-00295-2 Pub-Med Number: 37117221 Engineered whole lungs [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Cell Biology\" \/>\n<meta property=\"article:published_time\" content=\"2023-06-14T20:01:12+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-05-22T21:01:13+00:00\" \/>\n<meta name=\"author\" content=\"zkr7e@virginia.edu\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"zkr7e@virginia.edu\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/\"},\"author\":{\"name\":\"zkr7e@virginia.edu\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/#\\\/schema\\\/person\\\/b4929a1d4683383a392718e12166cd7f\"},\"headline\":\"Rational engineering of lung alveolar epithelium\",\"datePublished\":\"2023-06-14T20:01:12+00:00\",\"dateModified\":\"2026-05-22T21:01:13+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/\"},\"wordCount\":214,\"keywords\":[\"Intranet\"],\"articleSection\":[\"Featured Publications\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/\",\"url\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/\",\"name\":\"Rational engineering of lung alveolar epithelium - Department of Cell Biology\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/#website\"},\"datePublished\":\"2023-06-14T20:01:12+00:00\",\"dateModified\":\"2026-05-22T21:01:13+00:00\",\"author\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/#\\\/schema\\\/person\\\/b4929a1d4683383a392718e12166cd7f\"},\"breadcrumb\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2023\\\/06\\\/14\\\/rational-engineering-of-lung-alveolar-epithelium\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Rational engineering of lung alveolar epithelium\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/#website\",\"url\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/\",\"name\":\"Department of Cell Biology\",\"description\":\"University of Virginia School of Medicine\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/#\\\/schema\\\/person\\\/b4929a1d4683383a392718e12166cd7f\",\"name\":\"zkr7e@virginia.edu\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/eb05928a9c10d0bc86fc859e223e3e9cd7a535837367cf67c524db2a42f795d0?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/eb05928a9c10d0bc86fc859e223e3e9cd7a535837367cf67c524db2a42f795d0?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/eb05928a9c10d0bc86fc859e223e3e9cd7a535837367cf67c524db2a42f795d0?s=96&d=mm&r=g\",\"caption\":\"zkr7e@virginia.edu\"},\"url\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/author\\\/zkr7evirginia-edu\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Rational engineering of lung alveolar epithelium - Department of Cell Biology","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/","og_locale":"en_US","og_type":"article","og_title":"Rational engineering of lung alveolar epithelium - Department of Cell Biology","og_description":"UVA Author: Karen Hirschi Citation: Leiby KL, Yuan Y, Ng R, Raredon MSB, Adams TS, Baevova P, Greaney AM, Hirschi KK, Campbell SG, Kaminski N, Herzog EL, Niklason LE. Rational engineering of lung alveolar epithelium. NPJ Regen Med. 2023 Apr 28;8(1):22. doi: 10.1038\/s41536-023-00295-2. PMID: 37117221; PMCID: PMC10147714. DOI: https:\/\/doi.org\/10.1038\/s41536-023-00295-2 Pub-Med Number: 37117221 Engineered whole lungs [&hellip;]","og_url":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/","og_site_name":"Department of Cell Biology","article_published_time":"2023-06-14T20:01:12+00:00","article_modified_time":"2026-05-22T21:01:13+00:00","author":"zkr7e@virginia.edu","twitter_card":"summary_large_image","twitter_misc":{"Written by":"zkr7e@virginia.edu","Est. reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/#article","isPartOf":{"@id":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/"},"author":{"name":"zkr7e@virginia.edu","@id":"https:\/\/med.virginia.edu\/cell-biology\/#\/schema\/person\/b4929a1d4683383a392718e12166cd7f"},"headline":"Rational engineering of lung alveolar epithelium","datePublished":"2023-06-14T20:01:12+00:00","dateModified":"2026-05-22T21:01:13+00:00","mainEntityOfPage":{"@id":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/"},"wordCount":214,"keywords":["Intranet"],"articleSection":["Featured Publications"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/","url":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/","name":"Rational engineering of lung alveolar epithelium - Department of Cell Biology","isPartOf":{"@id":"https:\/\/med.virginia.edu\/cell-biology\/#website"},"datePublished":"2023-06-14T20:01:12+00:00","dateModified":"2026-05-22T21:01:13+00:00","author":{"@id":"https:\/\/med.virginia.edu\/cell-biology\/#\/schema\/person\/b4929a1d4683383a392718e12166cd7f"},"breadcrumb":{"@id":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/med.virginia.edu\/cell-biology\/2023\/06\/14\/rational-engineering-of-lung-alveolar-epithelium\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/med.virginia.edu\/cell-biology\/"},{"@type":"ListItem","position":2,"name":"Rational engineering of lung alveolar epithelium"}]},{"@type":"WebSite","@id":"https:\/\/med.virginia.edu\/cell-biology\/#website","url":"https:\/\/med.virginia.edu\/cell-biology\/","name":"Department of Cell Biology","description":"University of Virginia School of Medicine","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/med.virginia.edu\/cell-biology\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/med.virginia.edu\/cell-biology\/#\/schema\/person\/b4929a1d4683383a392718e12166cd7f","name":"zkr7e@virginia.edu","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/eb05928a9c10d0bc86fc859e223e3e9cd7a535837367cf67c524db2a42f795d0?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/eb05928a9c10d0bc86fc859e223e3e9cd7a535837367cf67c524db2a42f795d0?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/eb05928a9c10d0bc86fc859e223e3e9cd7a535837367cf67c524db2a42f795d0?s=96&d=mm&r=g","caption":"zkr7e@virginia.edu"},"url":"https:\/\/med.virginia.edu\/cell-biology\/author\/zkr7evirginia-edu\/"}]}},"_links":{"self":[{"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/posts\/107427","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/users\/1740"}],"replies":[{"embeddable":true,"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/comments?post=107427"}],"version-history":[{"count":1,"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/posts\/107427\/revisions"}],"predecessor-version":[{"id":107512,"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/posts\/107427\/revisions\/107512"}],"wp:attachment":[{"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/media?parent=107427"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/categories?post=107427"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/med.virginia.edu\/cell-biology\/wp-json\/wp\/v2\/tags?post=107427"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}