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@ARTICLE{Will:284769,
author = {P. A. Will and K. Kilian and K. Bieback and F. Fricke$^*$
and J. E. Berner and U. Kneser and C. Hirche},
title = {{L}ymphedema-{A}ssociated {F}ibroblasts {A}re {R}elated to
{F}ibrosis and {S}tage {P}rogression in {P}atients and a
{M}urine {M}icrosurgical {M}odel},
journal = {Plastic and reconstructive surgery},
volume = {154},
number = {4},
issn = {0032-1052},
address = {[Erscheinungsort nicht ermittelbar]},
publisher = {Ovid},
reportid = {DKFZ-2023-02080},
pages = {688e-700e},
year = {2024},
note = {2024 Oct 1;154(4):688e-700e},
abstract = {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.Whole skin samples of 35
murine subjects of a microsurgical-induced SL model and 12
patients with SL were collected and their fibroblasts were
isolated. These lymphedema-derived fibroblasts (LAF) were
cultured in a collagen I-poly-D-Lysine 3D hydrogel to mimic
skin conditions. Fibroblasts from non-lymphedema skin were
used as negative control and 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.In contrast to
normal skin fibroblasts, LAF exhibit α-SMA-positive stress
fibers and a reduced number of tight junctions in 3D
hydrogel conditions. The switch from normal E-cadherin high
phenotype to an N-cadherin high-E-cadherin low morphology
suggests epithelial to mesenchymal transition for expansion
and proliferation. This pathological behavior of LAF was
confirmed by live cell imaging analysis of invasion assays.
The significant activation of markers of the TGFBR2-Smad
pathway and collagen synthesis (HSP-47) in LAF supports EMT
phenotypic changes and previous findings relating to TGF-β1
and fibrosis with lymphedema.A characteristic SL
myofibroblast subpopulation was identified and
translationally related to fibrosis and TGF-β1-associated
stage progression. This SL-related subpopulation was termed
lymphedema-associated fibroblasts. A comprehensive
stage-related characterization is required to validate LAF
as a reliable biomarker for SL disease progression.},
cin = {F210},
ddc = {610},
cid = {I:(DE-He78)F210-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37832143},
doi = {10.1097/PRS.0000000000011141},
url = {https://inrepo02.dkfz.de/record/284769},
}