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

Mithun Sinha, Chandan K. Sen, Kanhaiya Singh, Amitava Das, Subhadip Ghatak, Brian Rhea, Britani Blackstone, Heather M. Powell, Savita Khanna and Sashwati Roy ()
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Mithun Sinha: The Ohio State University Wexner Medical Center
Chandan K. Sen: The Ohio State University Wexner Medical Center
Kanhaiya Singh: The Ohio State University Wexner Medical Center
Amitava Das: The Ohio State University Wexner Medical Center
Subhadip Ghatak: The Ohio State University Wexner Medical Center
Brian Rhea: The Ohio State University Wexner Medical Center
Britani Blackstone: The Ohio State University
Heather M. Powell: The Ohio State University
Savita Khanna: The Ohio State University Wexner Medical Center
Sashwati Roy: The Ohio State University Wexner Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-19

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03208-w

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