{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:04:43Z","timestamp":1777939483036,"version":"3.51.4"},"reference-count":102,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part C: Methods"],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:p>\n                    Notch is an evolutionary, conserved, cell\u2013cell signaling pathway that is central to several biological processes, from tissue morphogenesis to homeostasis. It is therefore not surprising that several genetic mutations of Notch components cause inherited human diseases, especially cardiovascular disorders. Despite numerous efforts, current\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    models are still insufficient to unravel the underlying mechanisms of these pathologies, hindering the development of utmost needed medical therapies. In this perspective review, we discuss the limitations of current murine models and outline how the combination of microphysiological systems (MPSs) and targeted computational models can lead to breakthroughs in this field. In particular, while MPSs enable the experimentation on human cells in controlled and physiological environments,\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    models can provide a versatile tool to translate the\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    findings to the more complex\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    setting. As a showcase example, we focus on Notch-related cardiovascular diseases, such as Alagille syndrome, Adams\u2013Oliver syndrome, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Impact statement<\/jats:title>\n                    <jats:p>\n                      In this review, a comprehensive overview of the limitations of current\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      models of genetic Notch cardiovascular diseases is provided, followed by a discussion over the potential of microphysiological systems and computational models in overcoming these limitations and in potentiating drug testing and modeling of these pathologies.\n                    <\/jats:p>\n                  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