The following is a summary of “Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations,” published in the June 2024 issue of Dermatology by Langbroek, et al.
Capillary malformations (CM), commonly known as port-wine stains, are congenital skin lesions marked by dilated capillaries and postcapillary venules. These malformations are the result of altered vascular endothelium function. Somatic genetic mutations, primarily in the endothelial cells of CMs, have been identified, creating opportunities for targeted therapies. However, there needs to be more mechanistic insight into pathophysiology and a lack of preclinical research methodologies. For a study, researchers sought to investigate the somatic genetic mutations and their functional impact on endothelial cells in patients with capillary malformations, aiming to develop a functional research model for CM pathophysiology.
In a monocenter exploratory study involving 17 adult patients with CMs, somatic sequence variants in the GNAQ (p.R183Q, p.R183G, or p.Q209R) or GNA11 (p.R183C) genes were identified. Primary endothelial cells were cultured from skin biopsies using an endothelial-selective cell isolation protocol. The cultured cells’ endothelial specificity was confirmed through vascular endothelial-cadherin immunostaining. Additionally, the angiogenic capacity of endothelial cells with the GNAQ (p.R183G) mutation was tested.
Patient-derived endothelial cells were successfully cultured in 3 of the 17 cases while maintaining endothelial specificity. The angiogenic capacity of endothelial cells with the GNAQ (p.R183G) mutation was assessed, revealing the potential of primary cells from CMs as a functional research model.
These proof-of-principle results demonstrated that primary endothelial cells isolated from CMs can serve as a functional research model to study the role of endothelial somatic mutations in the etiology of CMs. However, improved isolation and culture methodologies are essential to advance research in this field.
Reference: sciencedirect.com/science/article/pii/S0022202X23031159