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

Data:	2023
Resum:	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.
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Angiogenesis ; Endothelial cells ; Port-wine stains ; Sturge-Weber syndrome ; Vascular malformations
Publicat a:	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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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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