Vunjak-Novakovic, who heads the Laboratory for Stem Cells and Tissue Engineering, focuses on tissue engineering approaches to improving human health. Her lab was part of the first wave of the development of micro-sized human tissue platforms \u2013 called microphysiological systems or organs-on-a-chip \u2013 for modeling human pathophysiology and drug response. For this study, the engineers teamed up with colleagues at Columbia\u2019s Herbert Irving Comprehensive Cancer Center: Andrea Califano, the Clyde and Helen Wu Professor of Chemical and Systems Biology, Peter Sims, associate professor of systems biology, and Hanina Hibshoosh, professor of pathology & cell biology.\u00a0<\/p>\n
Ilaria Baldassarri, a PhD student at Columbia Engineering and one of the lead authors of the study, said she is excited about what the work demonstrates for the future of preclinical research: engineered human tissues that can complement what is learned from animal models. \u201cAs the FDA and NIH place growing emphasis on new approach methodologies, this study is a concrete example of what that shift can look like in practice, applied to one of cancer\u2019s most challenging hallmarks: metastasis,\u201d Baldassarri said.\u00a0<\/p>\n
Bone and lung, common sites of metastasis for breast cancer, and the vascular endothelium were engineered from induced pluripotent stem cells (iPSCs) using tissue-specific scaffold-bioreactor culture systems. The engineered tissues were maintained in individual compartments of the chip, which were each optimized for tissue maturation and long-term maintenance of functionality, and linked to each other by vascular circulation.\u00a0<\/p>\n
A selectively permeable endothelial barrier is a critical feature of this chip, as it separates tissue compartments from the vascular channel, as in the human body. Once the platform was established, the researchers introduced breast cancer cells into the vascular circulation to observe patterns of organ-specific colonization. In line with what happens inside the human body, cancer cells that typically gravitate towards the bone showed stronger bone colonization and induced more pronounced bone degeneration. In contrast, cancer cells that typically gravitate towards the lung caused greater disruption in the lung tissue and only modest colonization of bone. Distinct patterns of tissue colonization and secreted factors demonstrate that this device mimics key features of organ-specific metastasis observed in the human body.\u00a0<\/p>\n
In addition, a post-analysis of the engineered tissue revealed that cancer cells condition the distant organs to be more receptive to colonization. The team saw signs of this process \u2013 called pre-metastatic niche formation \u2013 across both tissue compartments.\u00a0<\/p>\n
\u201cThe key advantages of this advanced model of metastasis are that it is human and can be patient-specific,\u201d Vunjak-Novakovic said. \u201cIt faithfully mimics some of the key aspects of human metastasis that are otherwise largely inaccessible for direct study.\u201d\u00a0<\/p>\n
Source: Columbia University School of Engineering and Applied Science\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"Vunjak-Novakovic, who heads the Laboratory for Stem Cells and Tissue Engineering, focuses on tissue engineering approaches to improving…\n","protected":false},"author":2,"featured_media":598939,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[103,61,60,253897,253896],"class_list":["post-598938","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-ie","tag-ireland","tag-with-colleagues-including-califano_lab-and-psimslab-brled-by-cuseas-brled-by-columbiaseas-bsky-social","tag-x-led-by-gvnlab-at-cuseas"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/598938","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=598938"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/598938\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/598939"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=598938"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=598938"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=598938"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}