Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
Langbroek, Ginger Beau (University of Amsterdam)
Stor, Merem L.E. (University of Amsterdam)
Janssen, Vera (University of Amsterdam)
de Haan, Annett (University of Amsterdam)
Horbach, Sophie E.R. (University of Amsterdam)
Graupera, Mariona (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
van Noesel, Carel J.M. (University of Amsterdam)
van der Horst, Chantal M.A.M. (University of Amsterdam)
Wolkerstorfer, Albert (University of Amsterdam)
Huveneers, Sthephan (University of Amsterdam)

Date:	2023
Abstract:	Capillary malformations (CM) (port-wine stains) are congenital skin lesions that are characterized by dilated capillaries and postcapillary venules. CMs are caused by altered functioning of the vascular endothelium. Somatic genetic mutations have predominantly been identified in the endothelial cells of CMs, providing an opportunity for the development of targeted therapies. However, there is currently limited in-depth mechanistic insight into the pathophysiology and a lack of preclinical research approaches. In a monocenter exploratory study of 17 adult patients with CMs, we found somatic sequence variants in the GNAQ (p. R183Q, p. R183G, or p. Q209R) or GNA11 (p. R183C) genes. We applied an endothelial-selective cell isolation protocol to culture primary endothelial cells from skin biopsies from these patients. We successfully expanded patient-derived cells in culture in 3 of the 17 cases while maintaining endothelial specificity as demonstrated by vascular endothelial-cadherin immunostainings. In addition, we tested the angiogenic capacity of endothelial cells from a patient with a GNAQ (p. R183G) sequence substitution. These proof-of-principle results reveal that primary cells isolated from CMs may represent a functional research model to investigate the role of endothelial somatic mutations in the etiology of CMs, but improved isolation and culture methodologies are urgently needed to advance the field.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Angiogenesis ; Endothelial cells ; Port-wine stains ; Sturge-Weber syndrome ; Vascular malformations
Published in:	The Journal of investigative dermatology, 2023 , ISSN 1523-1747

DOI: 10.1016/j.jid.2023.10.033

12 p, 3.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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