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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Mithun Sinha & Chandan K. Sen & Kanhaiya Singh & Amitava Das & Subhadip Ghatak & Brian Rhea & Britani Blackstone & Heather M. Powell & Savita Khanna & Sashwati Roy, 2018. "Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue," Nature Communications, Nature, vol. 9(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03208-w
    DOI: 10.1038/s41467-018-03208-w
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    Cited by:

    1. Durba Pal & Subhadip Ghatak & Kanhaiya Singh & Ahmed Safwat Abouhashem & Manishekhar Kumar & Mohamed S El Masry & Sujit K. Mohanty & Ravichand Palakurti & Yashika Rustagi & Saba Tabasum & Dolly K. Kho, 2023. "Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Katarzyna M. Sitnik & Fran Krstanović & Natascha Gödecke & Ulfert Rand & Tobias Kubsch & Henrike Maaß & Yeonsu Kim & Ilija Brizić & Luka Čičin-Šain, 2023. "Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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