| Online-Ressource |
Verfasst von: | Will-Marks, Patrick [VerfasserIn]  |
| Kilian, Katja [VerfasserIn]  |
| Bieback, Karen [VerfasserIn]  |
| Fricke, Fabia [VerfasserIn]  |
| Berner, Juan Enrique [VerfasserIn]  |
| Kneser, Ulrich [VerfasserIn]  |
| Hirche, Christoph [VerfasserIn]  |
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 |
Lymphedema-associated fibroblasts are related to fibrosis and stage progression in patients and a murine microsurgical model / Will-Marks, Patrick [VerfasserIn]; October 2024 (Online-Ressource)