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Distinct fibroblast assemblies establish scarless regeneration.
Cell Rep. 45:116767 (2025)
Optimal tissue recovery requires coordinated fibroblast activity from deep fascia. Using multi-modal imaging of fascia explants from lineage-specific reporter mice, we tracked wound fibroblasts over 5 days, revealing their organization into supracellular assemblies-sprouting, reticulating, and clustering throughout healing. High-throughput screening of the Prestwick library against these fascia explants identified drugs modulating these behaviors, revealing a spectrum from fibrosis to scarless healing. Recovery phenotypes correlated with fibroblast sprouting, reticulation, and clustering rather than traditional extracellular matrix (ECM) deposition markers. We identified two therapeutic categories: compounds disrupting reticulation/clustering that inhibit scarring and compounds (fluvastatin, thiostrepton, fenbendazole) disrupting sprouting that blocked pro-inflammatory fibroblast/myofibroblast commitment, promoted angiogenesis, reduced inflammatory infiltration, and enabled scar-free regenerative healing with hair follicle papillae regrowth in mice. These findings establish fibroblast supracellular organization as fundamental to tissue recovery, providing novel therapeutic targets for wound healing and fibrotic disorders.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cd201 ; Cp: Cell Biology ; Cp: Immunology ; Procr ; Fascia ; Fibroblast ; Protein C Receptor ; Wound Healing; Fibrosis; Mechanisms
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 45,
Issue: 1,
Article Number: 116767
Publisher
Cell Press
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status
Peer reviewed
Institute(s)
Research Unit Signaling and Translation (SAT)
Grants
Deutscher Akademischer Austauschdienst (DAAD)
Consejo Nacional de Ciencia y Tecnologia (CONACYT)
Jiangxi Province Natural Science Foundation
National Natural Science Foundation of China
China Scholarship Council
Chinese Institutes for Medical Research
Consejo Nacional de Ciencia y Tecnologia (CONACYT)
Jiangxi Province Natural Science Foundation
National Natural Science Foundation of China
China Scholarship Council
Chinese Institutes for Medical Research