TY - JOUR
T1 - Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
AU - Langbroek, Ginger Beau
AU - Stor, Merel L. E.
AU - Janssen, Vera
AU - de Haan, Annett
AU - Horbach, Sophie E. R.
AU - Graupera, Mariona
AU - van Noesel, Carel J. M.
AU - van der Horst, Chantal M. A. M.
AU - Wolkerstorfer, Albert
AU - Huveneers, Stephan
N1 - Funding Information: We thank Cindy van Roomen, the Core Facility Genomics, and the Pathology Department of the Amsterdam University Medical Center for experimental support. This research was financially supported by the Netherlands Organization of Scientific Research (NWO OCENW.KLEIN.281) and the AMC Foundation awarded to SERH. Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Endothelial cells
KW - Port-wine stains
KW - Sturge-Weber syndrome
KW - Vascular malformations
UR - http://www.scopus.com/inward/record.url?scp=85180296652&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jid.2023.10.033
DO - https://doi.org/10.1016/j.jid.2023.10.033
M3 - Article
C2 - 38013159
SN - 0022-202X
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -