First Author | Sinha M | Year | 2018 |
Journal | Nat Commun | Volume | 9 |
Issue | 1 | Pages | 936 |
PubMed ID | 29507336 | Mgi Jnum | J:265510 |
Mgi Id | MGI:6149259 | Doi | 10.1038/s41467-018-03208-w |
Citation | Sinha M, et al. (2018) Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue. Nat Commun 9(1):936 |
abstractText | 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. |