{"id":12646,"date":"2017-07-12T05:54:52","date_gmt":"2017-07-12T05:54:52","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=12646"},"modified":"2017-07-12T05:54:52","modified_gmt":"2017-07-12T05:54:52","slug":"stem-cell-advance-brings-bioengineered-arteries-closer-reality","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/stem-cell-advance-brings-bioengineered-arteries-closer-reality\/","title":{"rendered":"Stem cell advance brings bioengineered arteries closer to reality"},"content":{"rendered":"<figure id=\"attachment_12647\" aria-describedby=\"caption-attachment-12647\" style=\"width: 775px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-12647 size-full\" src=\"http:\/\/revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg\" alt=\"\" width=\"775\" height=\"517\" title=\"\" srcset=\"https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg 775w, https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517-300x200.jpg 300w, https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517-768x512.jpg 768w\" sizes=\"auto, (max-width: 775px) 100vw, 775px\" \/><figcaption id=\"caption-attachment-12647\" class=\"wp-caption-text\">Morgridge Institute regenerative biology researchers Jue Zhang and Matt Brown examine a part for a new bioreactor designed to help grow arterial tissue. MORGRIDGE INSTITUTE FOR RESEARCH<\/figcaption><\/figure>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Stem cell biologists have tried unsuccessfully for years to produce cells that will give rise to functional arteries and give physicians new options to combat cardiovascular disease, the world\u2019s leading cause of death.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">But new techniques developed at the<\/span>\u00a0<a href=\"https:\/\/morgridge.org\/\" target=\"_blank\" rel=\"noopener\">Morgridge Institute for Research<\/a>\u00a0<span style=\"color: #000000;\">and the University of Wisconsin\u2013Madison have produced, for the first time, functional arterial cells at both the quality and scale to be relevant for disease modeling and clinical application.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Reporting in the July 10 issue of the journal\u00a0<\/span><a href=\"http:\/\/www.pnas.org\/\" target=\"_blank\" rel=\"noopener\"><em>Proceedings of the National Academy of Sciences<\/em><\/a><span style=\"color: #000000;\">, scientists in the lab of stem cell pioneer<\/span>\u00a0<a href=\"https:\/\/morgridge.org\/profile\/james-thomson\/\" target=\"_blank\" rel=\"noopener\">James Thomson\u00a0<\/a><span style=\"color: #000000;\">describe methods for generating and characterizing arterial endothelial cells \u2014 the cells that initiate artery development \u2014\u00a0that exhibit many of the specific functions required by the body.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Stem cell biologists have tried unsuccessfully for years to produce cells that will give rise to functional arteries and give physicians new options to combat cardiovascular disease, the world\u2019s leading cause of death.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">But new techniques developed at the<\/span>\u00a0<a href=\"https:\/\/morgridge.org\/\" target=\"_blank\" rel=\"noopener\">Morgridge Institute for Research<\/a>\u00a0<span style=\"color: #000000;\">and the University of Wisconsin\u2013Madison have produced, for the first time, functional arterial cells at both the quality and scale to be relevant for disease modeling and clinical application.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Reporting in the July 10 issue of the journal\u00a0<\/span><a href=\"http:\/\/www.pnas.org\/\" target=\"_blank\" rel=\"noopener\"><em>Proceedings of the National Academy of Sciences<\/em><\/a><span style=\"color: #000000;\">, scientists in the lab of stem cell pioneer\u00a0<\/span><a href=\"https:\/\/morgridge.org\/profile\/james-thomson\/\" target=\"_blank\" rel=\"noopener\">James Thomson\u00a0<\/a><span style=\"color: #000000;\">describe methods for generating and characterizing arterial endothelial cells \u2014 the cells that initiate artery development \u2014\u00a0that exhibit many of the specific functions required by the body.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Further, these cells contributed both to new artery formation and improved survival rate of mice used in a model for myocardial infarction. Mice treated with this cell line had an 83 percent survival rate, compared to 33 percent for controls.<\/span><\/p>\n<figure id=\"attachment_12648\" aria-describedby=\"caption-attachment-12648\" style=\"width: 300px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"size-medium wp-image-12648\" src=\"http:\/\/revoscience.com\/en\/wp-content\/uploads\/2017\/07\/endothelial-cell-markers-500x500-300x300.jpg\" alt=\"\" width=\"300\" height=\"300\" title=\"\" srcset=\"https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/endothelial-cell-markers-500x500-300x300.jpg 300w, https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/endothelial-cell-markers-500x500-150x150.jpg 150w, https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/endothelial-cell-markers-500x500.jpg 500w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption id=\"caption-attachment-12648\" class=\"wp-caption-text\">Arterial endothelial cells derived from human pluripotent stem cells are expressed in the red and white markers in this image. MORGRIDGE INSTITUTE FOR RESEARCH<\/figcaption><\/figure>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cThe cardiovascular diseases that kill people mostly affect the arteries, and no one has been able to make those kinds of cells efficiently before,\u201d says<\/span>\u00a0<a href=\"https:\/\/morgridge.org\/profile\/jue-zhang\/\" target=\"_blank\" rel=\"noopener\">Jue Zhang<\/a><span style=\"color: #000000;\">, a Morgridge assistant scientist and lead author. \u201cThe key finding here is a way to make arterial endothelial cells more functional and clinically useful.\u201d<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Cardiovascular disease accounts for one in every three deaths each year in the United States, according to the American Heart Association, and claims more lives each year than all forms of cancer combined. The Thomson lab has made arterial engineering one of its top research priorities.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The challenge is that generic endothelial cells are relatively easy to create, but they lack true arterial properties and thus have little clinical value, Zhang says.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The research team applied two pioneering technologies to the project. First, they used single-cell RNA sequencing to identify the signaling pathways critical for arterial endothelial cell differentiation. They found about 40 genes of optimal relevance. Second, they used CRISPR-Cas9 gene editing technology that allowed them to create reporter cell lines to monitor arterial differentiation in real time.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cWith this technology, you can test the function of these candidate genes and measure what percentage of cells are generating into our target arterial cells,\u201d says Zhang.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The research group developed a protocol around five key growth factors that make the strongest contributions to arterial cell development. They also identified some very common growth factors used in stem cell science, such as insulin, that surprisingly inhibit arterial endothelial cell differentiation.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cOur ultimate goal is to apply this improved cell derivation process to the formation of functional arteries that can be used in cardiovascular surgery,\u201d says Thomson, director of regenerative biology at Morgridge and a UW\u2013Madison professor of cell and regenerative biology. \u201cThis work provides valuable proof that we can eventually get a reliable source for functional arterial endothelial cells and make arteries that perform and behave like the real thing.\u201d<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Thomson\u2019s team, along with many UW\u2013Madison collaborators, is in the first year of a seven-year project supported by the National Institutes of Health on the feasibility of developing artery banks suitable for use in human transplantation.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">In many cases with vascular disease, patients lack suitable tissue from their own bodies for use in bypass surgeries. And growing arteries from an individual patient\u2019s stem cells would be cost prohibitive and take too long to be clinically useful.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The challenge will be not only to produce the arteries, but find ways to ensure they are compatible and not rejected by patients.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cNow that we have a method to create these cells, we hope to continue the effort using a more universal donor cell line,\u201d says Zhang. The lab will focus on cells banked from a unique population of people who are genetically compatible donors for a majority of the population.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Stem cell biologists have tried unsuccessfully for years to produce cells that will give rise to functional arteries and give physicians new options to combat cardiovascular disease, the world\u2019s leading cause of death. But new techniques developed at the\u00a0Morgridge Institute for Research\u00a0and the University of Wisconsin\u2013Madison have produced, for the first time, functional arterial cells [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":12647,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[16,17],"tags":[],"class_list":["post-12646","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-biology","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",775,517,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517-150x150.jpg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517-300x200.jpg",300,200,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517-768x512.jpg",750,500,true],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",750,500,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",775,517,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",775,517,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",775,517,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",775,517,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",600,400,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",600,400,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",735,490,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",540,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",95,63,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",640,427,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",96,64,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/07\/Jue-Zhang-and-Matt-Brown-in-lab-775x517.jpg",150,100,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"<a href=\"https:\/\/www.revoscience.com\/en\/category\/news\/biology\/\" rel=\"category tag\">Biology<\/a> <a href=\"https:\/\/www.revoscience.com\/en\/category\/news\/research\/\" rel=\"category tag\">Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/12646","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=12646"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/12646\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/12647"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=12646"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=12646"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=12646"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}