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Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
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Distinct fibroblast assemblies establish scarless regeneration.

Haifeng Ye1, Qing Yu2, Alvin John Kim Seong Lee3

  • 1Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, School of Basic Medical Sciences, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Jiangxi, China.

Cell Reports
|December 25, 2025
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Summary
This summary is machine-generated.

Tissue recovery depends on fibroblast organization in fascia. Targeting fibroblast supracellular assemblies with drugs promotes scar-free healing and regeneration, offering new therapeutic avenues for wound healing and fibrotic disorders.

Keywords:
CD201CP: cell biologyCP: immunologyPROCRfasciafibroblastprotein C receptorwound healing

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Regenerative Medicine

Background:

  • Optimal tissue recovery relies on coordinated fibroblast activity within deep fascia.
  • Fibroblast behavior and organization are critical for effective wound healing and preventing fibrosis.

Purpose of the Study:

  • To investigate the supracellular organization of fibroblasts during wound healing in fascia.
  • To identify therapeutic targets and compounds that modulate fibroblast behavior for improved tissue regeneration and reduced scarring.

Main Methods:

  • Utilized multi-modal imaging of fascia explants from lineage-specific reporter mice to track fibroblast organization over 5 days.
  • Performed high-throughput screening of the Prestwick drug library against fascia explants to identify compounds affecting fibroblast behavior.
  • Correlated observed recovery phenotypes with fibroblast supracellular organization markers and extracellular matrix (ECM) deposition.

Main Results:

  • Fibroblasts organized into supracellular assemblies, including sprouting, reticulating, and clustering, during wound healing.
  • Drug screening identified compounds that modulated these fibroblast behaviors, leading to a spectrum from fibrosis to scarless healing.
  • Therapeutic compounds disrupting fibroblast reticulation/clustering inhibited scarring, while those disrupting sprouting promoted scar-free regeneration, angiogenesis, and reduced inflammation.

Conclusions:

  • Fibroblast supracellular organization is fundamental to tissue recovery processes.
  • Targeting fibroblast supracellular assemblies offers novel therapeutic strategies for wound healing and fibrotic disorders.
  • Specific compounds identified can promote regenerative healing, including hair follicle papillae regrowth, by modulating fibroblast behavior.