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

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

Author information

1
Department of Surgery, Center for Regenerative Medicine and Cell Based Therapies, Comprehensive Wound Center, Davis Heart & Lung Institute, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
2
Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.
3
Department of Surgery, Center for Regenerative Medicine and Cell Based Therapies, Comprehensive Wound Center, Davis Heart & Lung Institute, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA. sashwati.roy@osumc.edu.

Abstract

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.

PMID:
29507336
PMCID:
PMC5838200
DOI:
10.1038/s41467-018-03208-w
[Indexed for MEDLINE]
Free PMC Article

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