Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue

Nat Commun. 2018 Mar 5;9(1):936. doi: 10.1038/s41467-018-03208-w.


Inflammation, following injury, induces cellular plasticity as an inherent component of physiological tissue repair. The dominant fate of wound macrophages is unclear and debated. Here we show that two-thirds of all granulation tissue fibroblasts, otherwise known to be of mesenchymal origin, are derived from myeloid cells which are likely to be wound macrophages. Conversion of myeloid to fibroblast-like cells is impaired in diabetic wounds. In cross-talk between keratinocytes and myeloid cells, miR-21 packaged in extracellular vesicles (EV) is required for cell conversion. EV from wound fluid of healing chronic wound patients is rich in miR-21 and causes cell conversion more effectively compared to that by fluid from non-healing patients. Impaired conversion in diabetic wound tissue is rescued by targeted nanoparticle-based delivery of miR-21 to macrophages. This work introduces a paradigm wherein myeloid cells are recognized as a major source of fibroblast-like cells in the granulation tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cellular Microenvironment
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Fibroblasts / metabolism
  • Granulation Tissue / cytology*
  • Humans
  • Keratinocytes / physiology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / metabolism
  • Myeloid Cells / physiology*
  • Transcriptome
  • Wound Healing*


  • MIRN21 microRNA, human
  • MicroRNAs