Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics.

Autor:	Doerfler P; Akribes Biomedical GmbH, Vienna, Austria. Electronic address: petra.doerfler@akribes-biomedical.at., Schoefmann N; Akribes Biomedical GmbH, Vienna, Austria., Cabral G; Akribes Biomedical GmbH, Vienna, Austria., Bauer W; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Berli MC; Balgrist University Hospital, Zurich, Switzerland; Technical Orthopedics, Diabetic Foot Consultation, Wound Outpatient Clinic, Spital Limmattal, Schlieren, Switzerland., Binder B; Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria., Borst C; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Botter S; Swiss Center for Musculoskeletal Biobanking, Balgrist Campus AG, Zurich, Switzerland., French LE; Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany., Goerge T; Department of Dermatology, University of Münster, Muenster, Germany., Hafner J; Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland., Hartmann D; Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany., Høgh A; Department of Vascular Surgery, Regionshospitalet Viborg, Viborg, Denmark., Hoetzenecker W; Department of Dermatology and Venerology, University of Linz, Linz, Austria., Holzer-Geissler JCJ; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria., Kamolz LP; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria., Kofler K; Department of Dermatology, Medical University of Tübingen, Tuebingen, Germany., Luger T; Department of Dermatology, University of Münster, Muenster, Germany., Nischwitz SP; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria., Popovits M; Department of Surgery, Barmherzige Brueder Hospital Graz, Graz, Austria; Privatklinik Graz Ragnitz, Graz, Austria., Rappersberger K; Klinik Landstrasse, Vienna, Austria., Restivo G; Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland., Schlager JG; Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany., Schmuth M; Department of Dermatology, Venerology and Allergology, Medical University of Innsbruck, Innsbruck, Austria., Stingl G; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Stockinger T; Klinik Landstrasse, Vienna, Austria., Stroelin A; Department of Dermatology, Medical University of Tübingen, Tuebingen, Germany., Stuetz A; Akribes Biomedical GmbH, Vienna, Austria., Umlauft J; Department of Dermatology, Venerology and Allergology, Medical University of Innsbruck, Innsbruck, Austria; Dermatology, Zellmed Medalp, Zell am Ziller, Austria., Weninger WP; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Wolff-Winiski B; Akribes Biomedical GmbH, Vienna, Austria. Electronic address: barbara.wolff-winiski@akribes-biomedical.at.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2024 Jul 01. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1016/j.jid.2024.05.029
Abstrakt:	Exudates of nonhealing wounds contain drivers of pathogenicity. We utilized >800 exudates from nonhealing and healing wounds of diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to (i) differentiate between healing and nonhealing wounds, (ii) follow the healing process of individual patients, and (iii) 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 nonhealing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo nonhealing 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 nonhealing wounds. Testing the wound therapeutics, PDGF and silver sulfadiazine, yielded responses in line with clinical experience and indicates the usefulness of the assay to search for and profile new therapeutics. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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