|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on May 30, 2024 |
Title |
Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics (NS79) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.
|
|
|
Overall design |
Independent of wound etiology, wound exudates from chronic wounds have inhibitory effects on proliferation of skin fibroblasts after incubation for 72h. To understand the early transcriptional response and the underlying molecular mechanism(s) leading to this inhibitory effect, primary skin fibroblasts were cultured for 6 hours with selected wound exudates from three patients with wounds of different etiologies (diabetic foot ulcer, mixed venous/arterial ulcer, and trauma/surgery). Wound exudates were used at concentrations that reduced fibroblast proliferation to 30% of control cells after 72h.
|
Web link |
https://www.jidonline.org/article/S0022-202X(24)01866-9/fulltext
|
|
|
Contributor(s) |
Doerfler P, Schoefmann N, Cabral G, Bauer W, Berli MC, Binder B, Borst C, Botter S, French LE, Goerge T, Hafner J, Hartmann D, Høgh A, Hoetzenecker W, Holzer-Geissler JJ, Kamolz LP, Kofler K, Luger T, Nischwitz SP, Popovits M, Rappersberger K, Restivo G, Schlager JG, Schmuth M, Stingl G, Stockinger T, Stroelin A, Stuetz A, Umlauft J, Weninger WP, Wolff-Winiski B |
Citation(s) |
38960086 |
|
Submission date |
May 29, 2024 |
Last update date |
Sep 02, 2024 |
Contact name |
Barbara Wolff-Winiski |
E-mail(s) |
barbara.wolff-winiski@akribes-biomedical.at
|
Organization name |
Akribes Biomedical
|
Street address |
Dr. Bohr-Gasse 7
|
City |
Vienna |
State/province |
Other (Non US) |
ZIP/Postal code |
1030 |
Country |
Austria |
|
|
Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
Samples (9)
|
GSM8295822 |
HDF, wound exudate WE78, replicate 1 |
GSM8295823 |
HDF, wound exudate WE78, replicate 2 |
GSM8295824 |
HDF, wound exudate WE78, replicate 3 |
GSM8295825 |
HDF, wound exudate WE43, replicate 1 |
GSM8295826 |
HDF, wound exudate WE43, replicate 2 |
GSM8295827 |
HDF, wound exudate WE43, replicate 3 |
|
This SubSeries is part of SuperSeries: |
GSE268641 |
Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics |
|
Relations |
BioProject |
PRJNA1117952 |
Supplementary file |
Size |
Download |
File type/resource |
GSE268639_NS79-2019_featurecounts.count.gene_Med-WE.txt.gz |
789.0 Kb |
(ftp)(http) |
TXT |
GSE268639_NS79-2019_featurecounts.cpm.gene_Med-WE.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
|
|
|
|
|