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Status: Bibliographieeintrag

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Verfasst von:Will-Marks, Patrick [VerfasserIn]   i
 Kilian, Katja [VerfasserIn]   i
 Bieback, Karen [VerfasserIn]   i
 Fricke, Fabia [VerfasserIn]   i
 Berner, Juan Enrique [VerfasserIn]   i
 Kneser, Ulrich [VerfasserIn]   i
 Hirche, Christoph [VerfasserIn]   i
Titel:Lymphedema-associated fibroblasts are related to fibrosis and stage progression in patients and a murine microsurgical model
Verf.angabe:Patrick A. Will, Msc, Katja Kilian, MD, Karen Bieback, PhD, Fabia Fricke, PhD, Juan Enrique Berner, FRCS, Ulrich Kneser, MD, Christoph Hirche, MD
E-Jahr:2024
Jahr:October 2024
Umfang:13 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 24.03.2025
Titel Quelle:Enthalten in: Plastic and reconstructive surgery
Ort Quelle:Philadelphia, Pa. : Lippincott Williams & Wilkins, 1946
Jahr Quelle:2024
Band/Heft Quelle:154(2024), 4, Seite 688e-700e
ISSN Quelle:1529-4242
Abstract:Background: - The driver of secondary lymphedema (SL) progression is chronic inflammation, which promotes fibrosis. Despite advances in preclinical research, a specific effector cell subpopulation as a biomarker for therapy response or stage progression is still missing for SL. - Methods: - Whole skin samples of 35 murine subjects of a microsurgically induced SL model and 12 patients with SL were collected and their fibroblasts were isolated. These lymphedema-associated fibroblasts (LAFs) were cultured in a collagen I-poly-D-lysine 3-dimensional hydrogel to mimic skin conditions. Fibroblasts from nonlymphedema skin were used as negative control and transforming growth factor β (TGF-β)-stimulated fibroblasts were used to recreate profibrotic myofibroblasts. Quantitative immunocytofluorescence confocal microscopy analysis and invasion functional assays were performed in all subpopulations and statistically compared. - Results: - In contrast to normal skin fibroblasts, LAFs exhibit α-smooth muscle actin-positive stress fibers and a reduced number of tight junctions in 3-dimensional hydrogel conditions. The switch from normal E-cadherinhigh phenotype to an N-cadherinhigh-E-cadherinlow morphology suggests epithelial-to-mesenchymal transition for expansion and proliferation. This pathologic behavior of LAF was confirmed by live cell imaging analysis of invasion assays. The significant activation of markers of the TGF-β receptor 2-Smad pathway and collagen synthesis (HSP-47 [heat shock protein 47]) in LAFs supports epithelial-to-mesenchymal transition phenotypic changes and previous findings relating to TGF-β1 and fibrosis with lymphedema. - Conclusions: - A characteristic SL myofibroblast subpopulation was identified and translationally related to fibrosis and TGF-β1-associated stage progression. This SL-related subpopulation was termed LAFs. A comprehensive stage-related characterization is required to validate LAFs as a reliable biomarker for SL disease progression. - Clinical Relevance Statement: - The authors identify a cellular effector for fibrosis and stage progression of secondary lymphedema as a possible biomarker for surgical indication and therapy response.
DOI:doi:10.1097/PRS.0000000000011141
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1097/PRS.0000000000011141
 Volltext: https://journals.lww.com/plasreconsurg/fulltext/2024/10000/lymphedema_associated_fibroblasts_are_related_to.19.aspx
 DOI: https://doi.org/10.1097/PRS.0000000000011141
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1920415149
Verknüpfungen:→ Zeitschrift

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