A2 Refereed review article in a scientific journal
Ex Vivo Models to Decipher the Molecular Mechanisms of Genetic Notch Cardiovascular Disorders
Authors: Ristori Tommaso, Sjöqvist Marika, Sahlgren Cecilia M
Publisher: MARY ANN LIEBERT, INC
Publication year: 2021
Journal: Tissue Engineering Part C Methods
Journal name in source: TISSUE ENGINEERING PART C-METHODS
Journal acronym: TISSUE ENG PART C-ME
Volume: 27
Issue: 3
First page : 167
Last page: 176
Number of pages: 10
ISSN: 1937-3384
eISSN: 1937-3392
DOI: https://doi.org/10.1089/ten.tec.2020.0327
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/53431470
Impact statementIn this review, a comprehensive overview of the limitations of current in vivo 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.Notch is an evolutionary, conserved, cell-cell 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 in vivo 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, in silico models can provide a versatile tool to translate the in vitro findings to the more complex in vivo setting. As a showcase example, we focus on Notch-related cardiovascular diseases, such as Alagille syndrome, Adams-Oliver syndrome, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Downloadable publication This is an electronic reprint of the original article. |  |
