A2 Vertaisarvioitu katsausartikkeli tieteellisessä lehdessä
Ex Vivo Models to Decipher the Molecular Mechanisms of Genetic Notch Cardiovascular Disorders
Tekijät: Ristori Tommaso, Sjöqvist Marika, Sahlgren Cecilia M
Kustantaja: MARY ANN LIEBERT, INC
Julkaisuvuosi: 2021
Journal: Tissue Engineering Part C Methods
Tietokannassa oleva lehden nimi: TISSUE ENGINEERING PART C-METHODS
Lehden akronyymi: TISSUE ENG PART C-ME
Vuosikerta: 27
Numero: 3
Aloitussivu: 167
Lopetussivu: 176
Sivujen määrä: 10
ISSN: 1937-3384
eISSN: 1937-3392
DOI: https://doi.org/10.1089/ten.tec.2020.0327
Rinnakkaistallenteen osoite: 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).
Ladattava julkaisu This is an electronic reprint of the original article. |  |
